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I was wondering what the difference is between the neural tube and the dorsal ventral cord.
I know that the neural tube forms during embryonic development from the ectoderm layer that folds inwards.
I thought that the neural tube gave rise to the central nervous system, however sometimes I see the following:
"the central nervous system develops from the hollow dorsal nerve cord"
for example: https://en.wikipedia.org/wiki/Dorsal_nerve_cord
What is the difference between the neural tube and the dorsal ventral cord or are they both the same? (talking about humans)
The terminology can be confusing, and I suspect the question you meant to ask was: what is the difference between the neural tube and dorsal nerve cord?
In vertebrates, the neural tube and the dorsal nerve cord are two names for the same structure. It develops into the brain and spinal cord.
Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system.
Source: Colas J-F and Schoenwolf GC. Towards a cellular and molecular understanding of neurulation. Developmental Dynamics. 2001. vol 221(2): 117-145.
This differs from invertebrates, some of which have a ventral nerve cord that does not invaginate and form a neural tube. As the name suggests, in contrast to vertebrates the nerve cord in these species is located ventrally.
Dorsal nerve cord = neural tube
Ventral nerve cord ≠ neural tube
The neural tube (Fig. 1) is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord. Its structure can be described in standard anatomical terms of location and their respective axes.
The dorsal - ventral axis (back to abdominal side) can be visualized by dissecting the neural tube transversely (Fig. 2). This axis is important for development. In the spinal cord, for instance, the dorsal region is the place where the spinal neurons receive input from sensory neurons, while the ventral region is where the motor neurons reside. In the middle are numerous interneurons that relay information between them. The polarity of the neural tube is induced by signals coming from its immediate environment. The dorsal pattern is imposed by the epidermis, while the ventral pattern is induced by the notochord (Gilbert, 2000).
Conversely, the anterior - posterior axis (head to tail) can be seen by a longitudinal transection (Fig. 1). Here, the important regions of the brain can be identified; the neural tube balloons into three primary vesicles, namely the forebrain (prosencephalon), midbrain (mesencephalon), and hindbrain (rhombencephalon). The prosencephalon becomes subdivided into the anterior telencephalon and the more caudal diencephalon (Gilbert, 2000).
Hence, regarding your question - there exists no such thing as a dorsal ventral cord.
Fig. 1. Anterior-to-posterior axis of the neural tube. Early primary structures (left) and adult structures (right). source: Gilbert (2000).
Fig. 2. Dorsal-ventral axis of the neural tube. source: Gilbert (2000).
- Gilbert, Developmental Biology. 6th ed. Sunderland (MA): Sinauer Associates (2000)
In the developing chordate (including vertebrates), the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into the closed neural tube. The ectodermal wall of which forms the rudiment of the nervous system. The centre of the tube is the neural canal.
Neural Tube Formation
Figure 1 | Neural tube closure in mouse and human embryos. Red labels indicate the NTDs associated with failure in specific closure events (red arrows). (Adapted from Copp & Greene 2010).
The neural tube serves as the embryos precursor to the central nervous system, and is therefore a requisite for the formation of the brain and spinal cord. The neural tube is formed during the process of neurulation in earlyeembryogenesis, beginning with neural plate (a thickening of dorsal surface ectoderm) formation and ending with neural tube closure. The neural plate contains a central indentation known as the neural groove, which gradually deepens leading to elevation of the neural folds, such that they’re ultimately juxtaposed towards one another at the midline their subsequent fusion leads to transformation of the neural groove into a closed canal termed the neural tube. Neural tube development is separated into two phases: primary and secondary.
In mammals, the closure of the neural tube is a multi-site process, where closure events initiate at separate location along the body axis (figure 1). In mice, closure begins at the border between the cervical spine and the hindbrain (closure 1) hours later, closure continues at the border between future forebrain and midbrain (closure2) and shortly after it restarts at the rostral boundary of the upcoming forebrain (closure 3). The regions of the neural folds that remain open (neuropores) after the initial sequence of closure events, continue to fuse together rostrocaudally in a bidirectional fashion (zippering), the end ofwwhich marks theccompletion primary neurulation (Copp 2005).
The formation of the spinal cord at the lower sacral and coccygeal areas depends on the subsequent process of secondary neurulation. The tail bud, at the caudal end of the mice contains a group of multipotent stem cells thatggive rise toccells with a neuralffate (Cambray & Wilson 2002). The most posterior of these cells undergo a process knows as canalization, leading to a unique arrangement of cell around a central cavity which is then termed the secondary neural tube. The lumens of both primary and secondary neural tubes are continuous with one another. Ultimately, the same multipotential stem cells found in the tail bud form the lateral sclerotomal cells that transform into sacral and coccygeal vertebrae.
There is a high degree of conservation of neurulation events between mammalian species nevertheless, there are some differences, notably the absence of closure 2 in human embryos. This absence of the closure point at the midbrain-forbrain boundary has been linked to the smaller midbrain in human embryo, which may have lead to the evolutionary elimination of closure 2 as an unnecessary process (Copp 2005).
Establishing an extracellular gradient of Shh
Shh is initially produced by the notochord, a rod-like population of mesodermal cells that acts as an organizing center for the overlying neural tissue and establishes an equivalent neural pattern on the left and right sides of the developing spinal cord(Echelard et al., 1993 Roelink et al., 1994). In amniotes, notochordal Shh induces a second center of Shh production within floor plate cells at the midline of the neural tube(Fig. 2A)(Marti et al., 1995 Roelink et al., 1995). In other vertebrates, the mechanism of floor plate induction appears to be less dependent on notochord-derived hedgehog (Hh) signaling (reviewed by Placzek and Briscoe, 2005). Several lines of evidence indicate that the spread of Shh through the ventral neural tube of the mouse and chick embryo establishes a gradient of activity that provides crucial spatial information necessary for pattern formation. As with other morphogens, the formation of a Shh gradient depends on three processes: (1) Shh production and secretion into the target field (2) its spread through the tissue and (3) its degradation and removal from the tissue. Each step is tightly regulated and involves dedicated molecular machinery.
Box 1. Shh as a graded morphogen
The morphogen concept dates back to the early twentieth century, but in its current formulation the theoretical work of Lewis Wolpert has been most influential (Wolpert, 1969 Wolpert, 1996). In particular, his `French Flag' model has become the conventional view of a morphogen. In this model, an idealized morphogen signal is proposed to subdivide a tissue into domains of different gene expression that correspond to the colors of the French flag. The signal is envisaged to be a secreted substance that emanates from a localized source and spreads through the tissue to establish a gradient of activity. Cells respond to this signal by inducing different target genes at different concentrations. In this view, a morphogen has two distinguishing features. First, it acts on cells at a distance from its source (the signaling range). Second, it induces differential gene expression in a concentration-dependent manner. Both of these criteria are met by Shh signaling in the neural tube: blockade of Shh signal transduction in neural progenitors some distance from the source of Shh disrupts DV patterning(Briscoe et al., 2001 Wijgerde et al., 2002) and,in vitro, different concentrations of recombinant Shh protein induce different profiles of gene expression in neural cells(Dessaud et al., 2007 Ericson et al., 1997).
Nevertheless, the conventional view of a morphogen has been challenged in recent years (Jaeger and Reinitz,2006 Pages and Kerridge,2000). The French Flag model assumes that the responding cells are more or less inert, passive recipients of the graded signal however, this assumption does not hold in the case of Shh signaling. Importantly, the response of cells to Shh signaling is fundamental to the generation of the morphogen response. First, Shh signaling regulates the expression of factors that influence its spread and stability consequently, the target tissue plays an active role in shaping the gradient (see text). Second, the upregulation of negative regulators of the pathway by Shh signaling results in the gradual adaptation of cells to ongoing signaling (see text). The adaptation process has the effect of transforming the extracellular gradient of Shh signaling to an intracellular period of signal transduction. This transformation is essential for the regulation of differential gene expression by Shh. These findings support the view that the morphogen activity of Shh in the neural tube is, in part, an emergent property that relies on both ligand and the response of the target tissue. Experimental findings for other morphogens and tissues have also led to modifications and elaborations to the conventional morphogen concept (Jaeger and Reinitz,2006).
Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6
Somites, segmented mesodermal units of the vertebrate embryo, are the precursors of adult skeletal muscle, bone and cartilage 1 . During embryogenesis, somite progenitor cells ingress through the primitive streak, move laterally to a paraxial position (alongside the body axis) and segment into epithelial somites 2 . Little is known about how this paraxial mesoderm tissue is specified 1 , 2 . We have previously described a mouse T-box gene, Tbx6 (ref. 3), which codes for a putative DNA-binding protein 4 , 5 . The embryonic pattern of expression of Tbx6 in somite precursor cells suggests that this gene may be involved in the specification of paraxial mesoderm 3 . We now report the creation of a mutation in Tbx6 that profoundly affects the differentiation of paraxial mesoderm. Irregular somites form in the neck region of mutant embryos, whereas more posterior paraxial tissue does not form somites but instead differentiates along a neural pathway, forming neural-tube-like structures that flank the axial neural tube. These paraxial tubes show dorsal/ventral patterning that is characteristic of the neural tube, and have differentiated motor neurons. These results indicate that Tbx6 is needed for cells to choose between a mesodermal and a neuronal differentiation pathway during gastrulation Tbx6 is essential for the specification of posterior paraxial mesoderm, and in its absence cells destined to form posterior somites differentiate along a neuronal pathway.
The origin of the idea of VENT cells
The idea of VENT cells originated from three different types of observations from histological sections of normal (i.e. unmanipulated) embryos. The first line of circumstantial evidence was that, shortly after the cranial nerves become morphologically identifiable, the ventral part of the neural tube is directly connected with the nerve, as if there was no physical barrier between their cell populations ( Sohal et al. 1996 Fig. 2A, cranial nerve III, motor). The ventral neural tube cells are continuous with the cells in the nerve and they appear to be morphologically identical (Fig. 2A). This continuity is only apparent in 3–4 consecutive sections, and is easily missed. Such physical and cellular continuity is transient, lasting about a day (Fig. 2B, cranial nerve III, motor). Basal lamina is thought to separate nerves from the neural tube, and continuity most likely arises from a transient breach ( Erickson, 1987 Niederlander & Lumsden, 1996 ). This observation raised the possibility that some ventral neural tube cells could emigrate through the exit/entry site of the nerves during the transient period of physical continuity.
Circumstantial evidence for the VENT cells from normal (i.e. experimentally unmanipulated) embryos. The ventral neural tube is directly connected transiently with the cranial nerves. (A,B) H&E-stained cross-sections of quail embryos. nt, midbrain neural tube III, the third cranial nerve. Continuity between the ventral neural tube and the nerve is seen at E3 (A, arrowheads) but not at E4 (B, arrowheads). Differential distribution of the HNK-1 antigen. (C,D) Sections through the hindbrain neural tube and fifth cranial nerve of quail embryos at E2.5 (C) and E3 (D), immunostained with anti-HNK-1 antibody. HNK-1 + cells are dark brown, whereas HNK-1 − cells are unstained. nt, neural tube. Prior to continuity with the neural tube, the ganglion comprises HNK-1 + cells (C). After continuity is established at E3, the ganglion also contains regions of HNK-1 − cells, continuous with the neural tube (D). The HNK-1 − cells are mainly in the central regions, whereas the HNK-1 + cells are mainly in the periphery of the ganglion. (E,F) Expression pattern of Islet-1. A section through the hindbrain neural tube and fifth cranial nerve of an E3.5 chick embryo is shown in bright-field (E) and fluorescence (F) after immunostaining with anti-Islet-1 antibody. fp, floor plate g, ganglion nt, neural tube. Arrowheads point to a trail of Islet-1 + cells in the ventral neural tube, extending into the ganglion. Scale bar, (A) 32 µm (B) 28 µm (C) 32 µm (D) 29 µm (E, F) 75 µm.
The second line of circumstantial evidence came from the pattern of expression of the HNK-1 antigen. HNK-1 is generally considered to be a good marker for neural crest and placodally derived cells ( Vincent & Thiery, 1984 ). Prior to the physical continuity between the ventral neural tube and the cranial nerves of the midbrain and hindbrain described above (and before axon ingrowth/outgrowth), the cranial nerves contain predominantly or exclusively HNK-1 + cells (Fig. 2C, cranial nerve V, mixed). For motor nerves, these HNK-1 + cells are neural crest-derived precursors of Schwann and supporting cells. For sensory and mixed nerves, the HNK-1 + cells are both neural crest and placodally derived. The neural crest cells give rise to neurons, Schwann and supporting cells, the placodally derived cells to neurons only ( Le Douarin & Kalcheim, 1999 ). After this continuity, the nerves clearly contain a heterogeneous mixture of cells, some HNK-1 + and others HNK-1 − (Fig. 2D, cranial nerve V, mixed). Further, the HNK-1 + cells were primarily located in the periphery of the nerves, whereas the HNK-1 − cells were primarily located in the central portion (Fig. 2D). It was reasoned that whereas the HNK-1 + cells represent neural crest and/or placodally derived cells (because both cell populations are HNK-1 + Vincent & Thiery, 1984 ), the HNK-1 − cells may have emigrated from the ventral part of the neural tube into the nerve during the transient period of physical continuity between them.
The third line of circumstantial evidence came from the expression pattern of the homeobox gene Islet-1. During the period of direct continuity between the ventral neural tube and the trigeminal ganglion, a trail of Islet-1 + cells extends ventrolaterally from the region adjacent to the floor plate up to the attachment point of the ganglion, and into the ganglion ( Sohal et al. 1996 Fig. 2E,F cranial nerve V, mixed), as if some Islet-1 + cells are destined to emigrate into the ganglion.
In summary, the transient lack of a barrier could allow ventral neural tube cells to emigrate into the nerve, and at least some of the HNK-1 − , Islet-1 + cells could be the emigrated cells. Such circumstantial evidence and reasoning formed the basis of the idea of VENT cells, which was subsequently investigated experimentally.
The neural tube develops in two ways: primary neurulation and secondary neurulation.
Primary neurulation divides the ectoderm into three cell types:
- The internally located neural tube
- The externally located epidermis
- The neural crest cells, which develop in the region between the neural tube and epidermis but then migrate to new locations
- Primary neurulation begins after the neural plate forms. The edges of the neural plate start to thicken and lift upward, forming the neural folds. The center of the neural plate remains grounded, allowing a U-shaped neural groove to form. This neural groove sets the boundary between the right and left sides of the embryo. The neural folds pinch in towards the midline of the embryo and fuse together to form the neural tube. Ώ]
- In secondary neurulation, the cells of the neural plate form a cord-like structure that migrates inside the embryo and hollows to form the tube.
Each organism uses primary and secondary neurulation to varying degrees.
- Neurulation in fish proceeds only via the secondary form.
- In avian species the posterior regions of the tube develop using secondary neurulation and the anterior regions develop by primary neurulation.
- In mammals, secondary neurulation begins around the 35th somite.
Mammalian neural tubes close in the head in the opposite order that they close in the trunk.
- In the head:
- Neural crest cells migrate
- Neural tube closes
- Overlying ectoderm closes
- In the trunk:
- Overlying ectoderm closes
- Neural tube closes
- Neural crest cells migrate
What is the difference between the neural tube and the dorsal ventral cord? - Biology
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into the closed neural tube. In humans, neural tube closure usually occurs by the fourth week of pregnancy (28th day after conception). The ectodermal wall of the tube forms the rudiment of the nervous system. The centre of the tube is the ''neural canal''.
The neural tube develops in two ways: primary neurulation and secondary neurulation. Primary neurulation divides the ectoderm into three cell types: * The internally located neural tube * The externally located epidermis * The neural crest cells, which develop in the region between the neural tube and epidermis but then migrate to new locations # Primary neurulation begins after the neural plate forms. The edges of the neural plate start to thicken and lift upward, forming the neural folds. The center of the neural plate remains grounded, allowing a U-shaped neural groove to form. This neural groove sets the boundary between the right and left sides of the embryo. The neural folds pinch in towards the midline of the embryo and fuse together to form the neural tube. Gilbert, Scott F. Developmental Biology Eighth Edition. Sunderland, Massachusetts: Sinauer Associates, Inc., 2006. # In secondary neurulation, the cells of the neural plate form a cord-like structure that migrates inside the embryo and hollows to form the tube. Each organism uses primary and secondary neurulation to varying degrees. * Neurulation in ''fish'' proceeds only via the secondary form. * In ''avian'' species the posterior regions of the tube develop using secondary neurulation and the anterior regions develop by primary neurulation. * In ''mammals'', secondary neurulation begins around the 35th somite. Mammalian neural tubes close in the head in the opposite order that they close in the trunk. * In the head: :#Neural crest cells migrate :#Neural tube closes :#Overlying ectoderm closes * In the trunk: :#Overlying ectoderm closes :#Neural tube closes :#Neural crest cells migrate
Four neural tube subdivisions each eventually develop into distinct regions of the central nervous system by the division of neuroepithelial cells: the forebrain (prosencephalon), the midbrain (mesencephalon), the hindbrain (rhombencephalon) and the spinal cord. * The ''prosencephalon'' further goes on to develop into the telencephalon (cerebrum) and the diencephalon (the optic vesicles and hypothalamus). * The ''mesencephalon'' stays as the midbrain. * The ''rhombencephalon'' develops into the metencephalon (the pons and cerebellum) and the myelencephalon (the medulla oblongata). For a short time, the neural tube is open both cranially and caudally. These openings, called neuropores, close during the fourth week in humans. Improper closure of the neuropores can result in neural tube defects such as anencephaly or spina bifida. The dorsal part of the neural tube contains the alar plate, which is associated primarily with sensation. The ventral part of the neural tube contains the basal plate, which is primarily associated with motor (i.e., muscle) control.The neural tube patterns along the dorsal-ventral axis to establish defined compartments of neural progenitor cells that lead to distinct classes of neurons. According to the French flag model of morphogenesis, this patterning occurs early in development and results from the activity of several secreted signaling molecules. Sonic hedgehog (Shh) is a key player in patterning the ventral axis, while bone morphogenic proteins (BMPs) and Wnt family members play an important role in patterning the dorsal axis. Other factors shown to provide positional information to the neural progenitor cells include fibroblast growth factors (FGFs) and retinoic acid. Retinoic acid is required ventrally along with Shh to induce Pax6 and Olig2 during differentiation of motor neurons. Three main ventral cell types are established during early neural tube development: the ''floor plate cells'', which form at the ventral midline during the neural fold stage as well as the more dorsally located motor neurons and interneurons. These cell types are specified by the secretion of the Shh from the notochord (located ventrally to the neural tube), and later from the floor plate cells. Shh acts as a morphogen, meaning that it acts in a concentration-dependent manner to specify cell types as it moves further from its source. The following is a proposed mechanism for how Shh patterns the ventral neural tube: A gradient of Shh that controls the expression of a group of homeodomain (HD) and basic Helix-Loop-Helix (bHLH) transcription factors is created. These transcription factors are grouped into two protein classes based on how Shh affects them. Class I is inhibited by Shh, whereas Class II is activated by Shh. These two classes of proteins then cross-regulate each other to create more-defined boundaries of expression. The different combinations of expression of these transcription factors along the dorsal-ventral axis of the neural tube are responsible for creating the identity of the neuronal progenitor cells. Five molecularly distinct groups of ventral neurons form from these neuronal progenitor cells in vitro. Also, the position at which these neuronal groups are generated ''in vivo'' can be predicted by the concentration of Shh required for their induction in vitro. Studies have shown that neural progenitors can evoke different responses based on the length of exposure to Shh, with a longer exposure time resulting in more ventral cell types. At the dorsal end of the neural tube, BMPs are responsible for neuronal patterning. BMP is initially secreted from the overlying ectoderm. A secondary signaling center is then established in the roof plate, the dorsal most structure of the neural tube. BMP from the dorsal end of the neural tube seems to act in the same concentration-dependent manner as Shh in the ventral end. This was shown using zebrafish mutants that had varying amounts of BMP signaling activity. Researchers observed changes in dorsal-ventral patterning, for example zebrafish deficient in certain BMPs showed a loss of dorsal sensory neurons and an expansion of interneurons.
What is the difference between the neural tube and the dorsal ventral cord? - Biology
The nervous system of a vertebrate develops from a structure known as the neural tube which then differentiates into the brain and spinal cord. The neural tube is formed very early on in the embryo, from a flat sheet which curves in on itself and then separates from the sheet to form a separate tube. This process is called neurulation.
Neurulation is influenced by the notochord, a structure that aligns itself through gastrulation. The notochord uses signalling molecules to induce ectodermal tissue to form the neural tube - the nature of these signals and the way in which they interact with ectoderm is relatively a conserved process through species.
The formation of the notochord is a very important step in the development of the neural tube: without the notochord the process of neurulation does not occur and thus the neural tube fails to develop. The notochord not only induces the neural tube - it also patterns it's anterior-posterior axis and dorsal-ventral axis. Neurulation occurs in two ways (primary and secondary) and often a combination of these two processes is used to close the neural tube.
(Image 1 - Human embryo at 7 weeks gestation , picture sourced from Wikipedia .)
The banner picture was sourced from the Society for Developmental Biology.
All information has been gathered from:
Gilbert S.F (2006). Developmental biology (8th ed). Sinauer.
Sanes D.H, Reh T.A, et al (2005). Development of the Nervous system (2nd ed). Academic Press .
Wolpert L, Beddington R, et al (2002). Principles of development (2nd ed). Oxford university press.
The Neural Tube
To begin, a sperm cell and an egg cell fuse to become a fertilized egg. The fertilized egg cell, or zygote, starts dividing to generate the cells that make up an entire organism. Sixteen days after fertilization, the developing embryo’s cells belong to one of three germ layers that give rise to the different tissues in the body. The endoderm, or inner tissue, is responsible for generating the lining tissues of various spaces within the body, such as the mucosae of the digestive and respiratory systems. The mesoderm, or middle tissue, gives rise to most of the muscle and connective tissues. Finally the ectoderm, or outer tissue, develops into the integumentary system (the skin) and the nervous system.
It is probably not difficult to see that the outer tissue of the embryo becomes the outer covering of the body. But how is it responsible for the nervous system? As the embryo develops, a portion of the ectoderm differentiates into a specialized region of neuroectoderm, which is the precursor for the tissue of the nervous system. Molecular signals induce cells in this region to differentiate into the neuroepithelium, forming a neural plate. The cells then begin to change shape, causing the tissue to buckle and fold inward (Figure 1).
A neural groove forms, visible as a line along the dorsal surface of the embryo. The ridge-like edge on either side of the neural groove is referred as the neural fold. As the neural folds come together and converge, the underlying structure forms into a tube just beneath the ectoderm called the neural tube. Cells from the neural folds then separate from the ectoderm to form a cluster of cells referred to as the neural crest, which runs lateral to the neural tube. The neural crest migrates away from the nascent, or embryonic, central nervous system (CNS) that will form along the neural groove and develops into several parts of the peripheral nervous system (PNS), including the enteric nervous tissue. Many tissues that are not part of the nervous system also arise from the neural crest, such as craniofacial cartilage and bone, and melanocytes.
Figure 1. Early Embryonic Development of Nervous System The neuroectoderm begins to fold inward to form the neural groove. As the two sides of the neural groove converge, they form the neural tube, which lies beneath the ectoderm. The anterior end of the neural tube will develop into the brain, and the posterior portion will become the spinal cord. The neural crest develops into peripheral structures.
At this point, the early nervous system is a simple, hollow tube. It runs from the anterior end of the embryo to the posterior end. Beginning at 25 days, the anterior end develops into the brain, and the posterior portion becomes the spinal cord. This is the most basic arrangement of tissue in the nervous system, and it gives rise to the more complex structures by the fourth week of development.
As the anterior end of the neural tube starts to develop into the brain, it undergoes a couple of enlargements the result is the production of sac-like vesicles. Similar to a child’s balloon animal, the long, straight neural tube begins to take on a new shape. Three vesicles form at the first stage, which are called primary vesicles.
These vesicles are given names that are based on Greek words, the main root word being enkephalon, which means “brain” (en- = “inside” kephalon = “head”). The prefix to each generally corresponds to its position along the length of the developing nervous system. The prosencephalon (pros- = “in front”) is the forward-most vesicle, and the term can be loosely translated to mean forebrain. The mesencephalon (mes- = “middle”) is the next vesicle, which can be called the midbrain. The third vesicle at this stage is the rhombencephalon. The first part of this word is also the root of the word rhombus, which is a geometrical figure with four sides of equal length (a square is a rhombus with 90° angles). Whereas prosencephalon and mesencephalon translate into the English words forebrain and midbrain, there is not a word for “four-sided-figure-brain.” However, the third vesicle can be called the hindbrain. One way of thinking about how the brain is arranged is to use these three regions—forebrain, midbrain, and hindbrain—which are based on the primary vesicle stage of development (Figure 2a).
The brain continues to develop, and the vesicles differentiate further (see Figure 2b). The three primary vesicles become five secondary vesicles. The prosencephalon enlarges into two new vesicles called the telencephalon and the diencephalon.
The telecephalon will become the cerebrum. The diencephalon gives rise to several adult structures two that will be important are the thalamus and the hypothalamus. In the embryonic diencephalon, a structure known as the eye cup develops, which will eventually become the retina, the nervous tissue of the eye called the retina. This is a rare example of nervous tissue developing as part of the CNS structures in the embryo, but becoming a peripheral structure in the fully formed nervous system.
The mesencephalon does not differentiate into any finer divisions. The midbrain is an established region of the brain at the primary vesicle stage of development and remains that way. The rest of the brain develops around it and constitutes a large percentage of the mass of the brain. Dividing the brain into forebrain, midbrain, and hindbrain is useful in considering its developmental pattern, but the midbrain is a small proportion of the entire brain, relatively speaking.
The rhombencephalon develops into the metencephalon and myelencephalon. The metencephalon corresponds to the adult structure known as the pons and also gives rise to the cerebellum. The cerebellum (from the Latin meaning “little brain”) accounts for about 10 percent of the mass of the brain and is an important structure in itself. The most significant connection between the cerebellum and the rest of the brain is at the pons, because the pons and cerebellum develop out of the same vesicle. The myelencephalon corresponds to the adult structure known as the medulla oblongata. The structures that come from the mesencephalon and rhombencephalon, except for the cerebellum, are collectively considered the brain stem, which specifically includes the midbrain, pons, and medulla.
Figure 2. Primary and Secondary Vesicle Stages of Development The embryonic brain develops complexity through enlargements of the neural tube called vesicles (a) The primary vesicle stage has three regions, and (b) the secondary vesicle stage has five regions.
Spinal Cord Development
While the brain is developing from the anterior neural tube, the spinal cord is developing from the posterior neural tube. However, its structure does not differ from the basic layout of the neural tube. It is a long, straight cord with a small, hollow space down the center. The neural tube is defined in terms of its anterior versus posterior portions, but it also has a dorsal–ventral dimension. As the neural tube separates from the rest of the ectoderm, the side closest to the surface is dorsal, and the deeper side is ventral. As the spinal cord develops, the cells making up the wall of the neural tube proliferate and differentiate into the neurons and glia of the spinal cord. The dorsal tissues will be associated with sensory functions, and the ventral tissues will be associated with motor functions.
Relating Embryonic Development to the Adult Brain
Embryonic development can help in understanding the structure of the adult brain because it establishes a framework on which more complex structures can be built. First, the neural tube establishes the anterior–posterior dimension of the nervous system, which is called the neuraxis. The embryonic nervous system in mammals can be said to have a standard arrangement. Humans (and other primates, to some degree) make this complicated by standing up and walking on two legs. The anterior–posterior dimension of the neuraxis overlays the superior–inferior dimension of the body. However, there is a major curve between the brain stem and forebrain, which is called the cephalic flexure. Because of this, the neuraxis starts in an inferior position—the end of the spinal cord—and ends in an anterior position, the front of the cerebrum. If this is confusing, just imagine a four-legged animal standing up on two legs. Without the flexure in the brain stem, and at the top of the neck, that animal would be looking straight up instead of straight in front (Figure 3).
Figure 3. Human Neuraxis The mammalian nervous system is arranged with the neural tube running along an anterior to posterior axis, from nose to tail for a four-legged animal like a dog. Humans, as two-legged animals, have a bend in the neuraxis between the brain stem and the diencephalon, along with a bend in the neck, so that the eyes and the face are oriented forward.
In summary, the primary vesicles help to establish the basic regions of the nervous system: forebrain, midbrain, and hindbrain. These divisions are useful in certain situations, but they are not equivalent regions. The midbrain is small compared with the hindbrain and particularly the forebrain. The secondary vesicles go on to establish the major regions of the adult nervous system that will be followed in this text. The telencephalon is the cerebrum, which is the major portion of the human brain.
The diencephalon continues to be referred to by this Greek name, because there is no better term for it (dia– = “through”). The diencephalon is between the cerebrum and the rest of the nervous system and can be described as the region through which all projections have to pass between the cerebrum and everything else.
The brain stem includes the midbrain, pons, and medulla, which correspond to the mesencephalon, metencephalon, and myelencephalon. The cerebellum, being a large portion of the brain, is considered a separate region. Table 1 connects the different stages of development to the adult structures of the CNS.
One other benefit of considering embryonic development is that certain connections are more obvious because of how these adult structures are related. The retina, which began as part of the diencephalon, is primarily connected to the diencephalon. The eyes are just inferior to the anterior-most part of the cerebrum, but the optic nerve extends back to the thalamus as the optic tract, with branches into a region of the hypothalamus.
There is also a connection of the optic tract to the midbrain, but the mesencephalon is adjacent to the diencephalon, so that is not difficult to imagine. The cerebellum originates out of the metencephalon, and its largest white matter connection is to the pons, also from the metencephalon. There are connections between the cerebellum and both the medulla and midbrain, which are adjacent structures in the secondary vesicle stage of development. In the adult brain, the cerebellum seems close to the cerebrum, but there is no direct connection between them.
Another aspect of the adult CNS structures that relates to embryonic development is the ventricles—open spaces within the CNS where cerebrospinal fluid circulates. They are the remnant of the hollow center of the neural tube. The four ventricles and the tubular spaces associated with them can be linked back to the hollow center of the embryonic brain (see Table 1).
|Table 1. Stages of Embryonic Development|
|Neural tube||Primary vesicle stage||Secondary vesicle stage||Adult structures||Ventricles|
|Anterior neural tube||Prosencephalon||Telencephalon||Cerebrum||Lateral ventricles|
|Anterior neural tube||Prosencephalon||Diencephalon||Diencephalon||Third ventricle|
|Anterior neural tube||Mesencephalon||Mesencephalon||Midbrain||Cerebral aqueduct|
|Anterior neural tube||Rhombencephalon||Metencephalon||Pons cerebellum||Fourth ventricle|
|Anterior neural tube||Rhombencephalon||Myelencephalon||Medulla||Fourth ventricle|
|Posterior neural tube||Spinal cord||Central canal|
Disorders of the Nervous System
Early formation of the nervous system depends on the formation of the neural tube. A groove forms along the dorsal surface of the embryo, which becomes deeper until its edges meet and close off to form the tube. If this fails to happen, especially in the posterior region where the spinal cord forms, a developmental defect called spina bifida occurs. The closing of the neural tube is important for more than just the proper formation of the nervous system. The surrounding tissues are dependent on the correct development of the tube. The connective tissues surrounding the CNS can be involved as well. There are three classes of this disorder: occulta, meningocele, and myelomeningocele (Figure 4).
Figure 4. Spinal Bifida (a) Spina bifida is a birth defect of the spinal cord caused when the neural tube does not completely close, but the rest of development continues. The result is the emergence of meninges and neural tissue through the vertebral column. (b) Fetal myelomeningocele is evident in this ultrasound taken at 21 weeks.
The first type, spina bifida occulta, is the mildest because the vertebral bones do not fully surround the spinal cord, but the spinal cord itself is not affected. No functional differences may be noticed, which is what the word occulta means it is hidden spina bifida.
The other two types both involve the formation of a cyst—a fluid-filled sac of the connective tissues that cover the spinal cord called the meninges. “Meningocele” means that the meninges protrude through the spinal column but nerves may not be involved and few symptoms are present, though complications may arise later in life. “Myelomeningocele” means that the meninges protrude and spinal nerves are involved, and therefore severe neurological symptoms can be present.
Often surgery to close the opening or to remove the cyst is necessary. The earlier that surgery can be performed, the better the chances of controlling or limiting further damage or infection at the opening. For many children with meningocele, surgery will alleviate the pain, although they may experience some functional loss. Because the myelomeningocele form of spina bifida involves more extensive damage to the nervous tissue, neurological damage may persist, but symptoms can often be handled. Complications of the spinal cord may present later in life, but overall life expectancy is not reduced.
Vertebrate Axis Formation
Through the expression patterns of different genes, the three axes of the body are established, aiding in tissue and organ development.
Describe the formation of body axes in vertebrates
- As an animal develops, it must organize its internal and external structures such that the anterior/posterior (forward/backward), dorsal / ventral (back/belly), and lateral/medial (side/middle) axes are correctly determined.
- Proteins that are part of the Wnt signaling pathway help determine the anterior/posterior axis by guiding the axons of the spinal cord in an anterior/posterior direction.
- Together with the sonic hedgehog (Shh) protein, Wnt determines the dorsal/ventral axis Wnt levels are highest in the dorsal region and lessen toward the ventral region, while Shh levels are highest in the ventral region and lessen toward the dorsal region.
- dorsal: with respect to, or concerning the side in which the backbone is located, or the analogous side of an invertebrate
- ventral: on the front side of the human body, or the corresponding surface of an animal, usually the lower surface
- notochord: a flexible rodlike structure that forms the main support of the body in the lowest chordates a primitive spine
- Wnt signaling pathway: a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell
Vertebrate Axis Formation
Even as the germ layers form, the ball of cells still retains its spherical shape. However, animal bodies have lateral-medial (toward the side-toward the midline), dorsal-ventral (toward the back-toward the belly), and anterior-posterior (toward the front-toward the back) axes. As the body forms, it must develop in such a way that cells, tissues, and organs are organized correctly along these axes.
Body axes: Animal bodies have three axes for symmetry: anterior/posterior (front/behind), dorsal/ventral (back/belly), and lateral/medial (side/middle).
How are these established? In one of the most seminal experiments ever to be carried out in developmental biology, Spemann and Mangold took dorsal cells from one embryo and transplanted them into the belly region of another embryo. They found that the transplanted embryo now had two notochords: one at the dorsal site from the original cells and another at the transplanted site. This suggested that the dorsal cells were genetically programmed to form the notochord and define the dorsal-ventral axis. Since then, researchers have identified many genes that are responsible for axis formation. Mutations in these genes leads to the loss of symmetry required for organism development. Many of these genes are involved in the Wnt signaling pathway.
In early embryonic development, the formation of the primary body axes is a crucial step in establishing the overall body plan of each particular organism. Wnt signaling can be implicated in the formation of the anteroposterior and dorsoventral axes. Wnt signaling activity in anterior-posterior development can be seen in several organisms including mammals, fish, and frogs. Wnt signaling is also involved in the axis formation of specific body parts and organ systems that are a part of later development. In vertebrates, sonic hedgehog (Shh) and Wnt morphogenetic signaling gradients establish the dorsoventral axis of the central nervous system during neural tube axial patterning. High Wnt signaling establishes the dorsal region while high Shh signaling indicates in the ventral region. Wnt is also involved in the dorsal-ventral formation of the central nervous system through its involvement in axon guidance. Wnt proteins guide the axons of the spinal cord in an anterior-posterior direction. Wnt is also involved in the formation of the limb dorsal-ventral axis. Specifically, Wnt7a helps produce the dorsal patterning of the developing limb.