Floor plate

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Floor plate
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The floor plate separates the left and right basal plates of the developing neural tube.
Details
Precursor Notochord
System Nervous system
Anatomical terminology

The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly Drosophila and the nematode C. elegans . Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube. [1] [2] [3]

Contents

Induction

Induction of the floor plate during embryogenesis of vertebrate embryos has been studied extensively in chick and zebrafish and occurs as a result of a complex signaling network among tissues, the details of which have yet to be fully refined. Currently there are several competing lines of thought. First, floor plate differentiation may be mediated by inductive signaling from the underlying notochord, an axial mesoderm derived signaling structure. This is supported experimentally in chick, in which floor plate induction, as well as associative ventral nervous tissue differentiation, is mediated by the secreted signaling molecule sonic hedgehog (Shh). Shh is expressed in a gradient with highest concentration localized in the notochord and floor plate. In vitro tissue grafting experiments show that removal of this molecule prevents differentiation of the floor plate, whereas its ectopic expression induces differentiation of floor plate cells. [4] An alternative view proposes that neural tube floor plate cells stem from precursor cells which migrate directly from axial mesoderm. Through chick – quail hybrid experiments as well as genetic interaction experiments in zebrafish, it appears that notochord and floor plate cells originate from a common precursor. Furthermore, in zebrafish, Nodal signaling is required for differentiation of medial floor plate cells whereas Shh is expendable. These data may indicate that the floor plate induction mechanism in amniotes and anamniotes differs. [5] To reconcile these differences, a dual-mode induction model has been proposed in chick. In this model, exclusively ectodermal cells are induced to become medial floor plate during gastrulation by prechordal mesoderm, possibly through Nodal signaling. Later in development during neurulation, extended contact and interaction between notochord and fated floor plate cells causes differentiation, suggesting a cooperative effect between Nodal and Shh signaling. [6]

Axon guidance

In the development of the central nervous system, the decision of a neuron to cross or not cross the midline is critical. In vertebrates, this choice is mediated by the floor plate, and enables the embryo to develop successful left and right body halves with respect to nervous tissue. For example, while ipsilateral neurons do not cross the midline, commissural neurons cross the midline forming a single commissure. These particular neurons develop in the dorsal region of the neural tube and travel ventrally toward the floor plate. Upon reaching the floor plate, commissural neurons cross through the structure to emerge on the opposite side of the neural tube, whereupon they project anteriorly or posteriorly within the tube. [7]

Crossing of commissural axons across the midline in vertebrates is mediated by signaling in the floor plate of the neural tube. On the left panel an axon initiates its projection within the tube. On the right panel, the neuron initially receives chemoattractive signaling from netrin ligands and chemorepellents from slit ligands (1). When the neuron commits to crossing, Robo-3 inhibits the repulsion signal received by Robo-1/2 from slit, allowing attraction (2). After crossing, Robo-1/2 is upregulated and again inhibits crossing via the ligand slit (3). FPimage.jpg
Crossing of commissural axons across the midline in vertebrates is mediated by signaling in the floor plate of the neural tube. On the left panel an axon initiates its projection within the tube. On the right panel, the neuron initially receives chemoattractive signaling from netrin ligands and chemorepellents from slit ligands (1). When the neuron commits to crossing, Robo-3 inhibits the repulsion signal received by Robo-1/2 from slit, allowing attraction (2). After crossing, Robo-1/2 is upregulated and again inhibits crossing via the ligand slit (3).

The signaling molecules guiding the growth and projections of commissural neurons have well studied homologs in invertebrates. In the Netrin/DCC chemoattraction pathway the C. elegans homologs are Unc-6/Unc-40 and Unc-5 while the Drosophila homologs are Netrin-A and Netrin-B/Frazzled and Dunc5. In the Slit/Robo chemoreppelant pathway the C. elegans homologs are Slt-1/Sax-3 whereas the Drosophila homologs are also known as Slit/Robo(1-3). [7]

Glial fate mapping

In the central nervous system (CNS), overall cell fate mapping is typically directed by the sonic hedgehog (Shh) morphogen signaling pathway. In the spinal cord, Shh is directed by both the notochord and floor plate regions which ultimately drives the organization of neural and glial progenitor populations. The specific glial populations impacted by Shh in these two regions include oligodendrocyte precursor cells (OPCs), oligodendrocytes, NG2+ cells, microglia, and astrocytes. [13] The floor plate (FP) region of the spinal cord individually contributes to gliogenesis, or the formation of glial cells. Traditionally, progenitor cells are driven from their progenitor expansion phase, to the neurogenic phase, and ultimately to the gliogenic phase. From the gliogenic phase, the former progenitor cells can then become astrocytes, oligodendrocytes, or other more specialized glial cell types. Recently, there have been efforts to use conditional mutagenesis to selectively inactivate the Shh pathway specifically in the FP region to identify different roles of molecules involved in oligodendrocyte cell fate. Oligodendrocytes are the cells responsible for myelinating axons in the CNS.

Shh regulates Gli processing through two proteins, Ptch1 and Smo. [14] When Shh is not active, Ptch1 is responsible for suppressing the pathway through the inhibition of Smo. Smo is crucial to the overall transduction of signal of the Shh pathway. If Smo is inhibited, the Shh pathway is also inactive, which ultimately represses gliogenesis. Specific factors such as Gli3 are required for oligodendrocyte cell fate. Since Shh regulates Gli processing, if Smo is compromised or inhibited by Ptch1, this inactivates the Shh pathway and prevents Gli processing which disrupts glial cell fate mapping. Shh signaling in the FP region is very important because it needs to be active in order for gliogenesis to occur. If Shh is inactivated within the FP region and activated in other regions of the spinal cord such as the Dbx or pMN domains, gliogenesis is compromised. But, when Shh is active in the FP region, gliogenesis is activated and glial cells begin migrating to their targeted destinations to function.

Spinal cord injury and axon regeneration

The floor plate region aids in axon guidance, glial fate mapping, and embryogenesis. If this area of the spinal cord becomes injured, there could be serious complications to all contributing functions of this region, namely limited proliferation and production of the glial cells responsible for myelination and phagocytosis in the CNS. Spinal cord injury (SCI) also most often results in axon denudation or severance. Wnt signaling is a common signaling pathway involved in injury cases. Wnt signaling regulates regeneration after spinal cord injury. Immediately following injury, Wnt expression dramatically increases. [15] Axon guidance is driven by Netrin-1 [8] in the FP region of the spinal cord. During injury cases, specifically cases of axon severance, Wnt signaling is upregulated and axons begin to initiate regeneration and the axons are reguided through the FP regions using Shh and Wnt signaling pathways.

The spinal cord ependymal cells also reside in the FP region of the spinal cord. These cells are a neural stem cell population responsible for repopulating lost cells during injury. These cells have the capacity to differentiate into progenitor glial populations. During injury, a factor entitled Akhirin is secreted in the FP region. During spinal cord development, Akhirin is expressed solely on ependymal stem cells with latent stem cell properties and plays a key role in the development of the spinal cord. In the absence of Akhirin, stemness of these ependymal cells is not regulated. [16] Injury compromises Akhirin expression and regulation and the cells of the FP region cannot properly be restored by the ependymal stem cell populations.

Related Research Articles

The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

Neural tube Developmental precursor to the central nervous system

In the developing chordate, 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. The ectodermal wall of the tube forms the rudiment of the nervous system. The centre of the tube is the neural canal.

Sonic hedgehog protein Protein encoded by the SHH gene in the species Homo sapiens

Sonic hedgehog protein(SHH) is encoded for by the SHH gene. The protein is named after the character Sonic the Hedgehog.

Retinal ganglion cell Type of cell within the eye

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.

Neuromeres are morphologically or molecularly defined transient segments of the early developing brain. Rhombomeres are such segments that make up the rhombencephalon or hindbrain. More controversially, some argue that there exist early developmental segments that give rise to structures of the midbrain (mesomeres) and forebrain (prosomeres).

Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research.

Netrin Class of proteins involved in axon guidance

Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin.

Alpha motor neuron

Alpha (α) motor neurons (also called alpha motoneurons), are large, multipolar lower motor neurons of the brainstem and spinal cord. They innervate extrafusal muscle fibers of skeletal muscle and are directly responsible for initiating their contraction. Alpha motor neurons are distinct from gamma motor neurons, which innervate intrafusal muscle fibers of muscle spindles.

Netrin receptor DCC

Netrin receptor DCC, also known as DCC, or colorectal cancer suppressor is a protein which in humans is encoded by the DCC gene. DCC has long been implicated in colorectal cancer and its previous name was Deleted in colorectal carcinoma. Netrin receptor DCC is a single transmembrane receptor.

Subcommissural organ

The subcommissural organ (SCO) is one of the circumventricular organs of the brain. It is a small glandular structure that is located in the posterior region of the third ventricle, near the entrance of the cerebral aqueduct.

Pioneer axon is the classification given to axons that are the first to grow in a particular region. They originate from pioneer neurons, and have the main function of laying down the initial growing path that subsequent growing axons, dubbed follower axons, from other neurons will eventually follow.

Roundabout family

The Roundabout (Robo) family of proteins are single-pass transmembrane receptors that are highly conserved across many branches of the animal kingdom, from C. elegans to humans. They were first discovered in Drosophila, through a mutant screen for genes involved in axon guidance. The Drosophila roundabout mutant was named after its phenotype, which resembled the circular traffic junctions. The Robo receptors are most well known for their role in the development of the nervous system, where they have been shown to respond to secreted Slit ligands. One well-studied example is the requirement for Slit-Robo signaling in regulation of axonal midline crossing. Slit-Robo signaling is also critical for many neurodevelopmental processes including formation of the olfactory tract, the optic nerve, and motor axon fasciculation. In addition, Slit-Robo signaling contributes to cell migration and the development of other tissues such as the lung, kidney, liver, muscle and breast. Mutations in Robo genes have been linked to multiple neurodevelopmental disorders in humans.

Spinal cord Long, tubular central nervous system structure in the vertebral column

The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column. It encloses the central canal of the spinal cord, which contains cerebrospinal fluid. The brain and spinal cord together make up the central nervous system (CNS). In humans, the spinal cord begins at the occipital bone, passing through the foramen magnum and entering the spinal canal at the beginning of the cervical vertebrae. The spinal cord extends down to between the first and second lumbar vertebrae, where it ends. The enclosing bony vertebral column protects the relatively shorter spinal cord. It is around 45 cm (18 in) long in adult men and around 43 cm (17 in) long in adult women. The diameter of the spinal cord ranges from 13 mm in the cervical and lumbar regions to 6.4 mm in the thoracic area.

Slit is a family of secreted extracellular matrix proteins which play an important signalling role in the neural development of most bilaterians. While lower animal species, including insects and nematode worms, possess a single Slit gene, humans, mice and other vertebrates possess three Slit homologs: Slit1, Slit2 and Slit3. Human Slits have been shown to be involved in certain pathological conditions, such as cancer and inflammation.

Gliogenesis is the generation of non-neuronal glia populations derived from multipotent neural stem cells.

Chondroitin sulfate proteoglycan

Chondroitin sulfate proteoglycans (CSPGs) are proteoglycans consisting of a protein core and a chondroitin sulfate side chain. They are known to be structural components of a variety of human tissues, including cartilage, and also play key roles in neural development and glial scar formation. They are known to be involved in certain cell processes, such as cell adhesion, cell growth, receptor binding, cell migration, and interaction with other extracellular matrix constituents. They are also known to interact with laminin, fibronectin, tenascin, and collagen. CSPGs are generally secreted from cells.

Slit-Robo is the name of a cell signaling protein complex with many diverse functions including axon guidance and angiogenesis.

Tropic cues involved in growth cone guidance

The growth cone is a highly dynamic structure of the developing neuron, changing directionality in response to different secreted and contact-dependent guidance cues; it navigates through the developing nervous system in search of its target. The migration of the growth cone is mediated through the interaction of numerous trophic and tropic factors; netrins, slits, ephrins and semaphorins are four well-studied tropic cues (Fig.1). The growth cone is capable of modifying its sensitivity to these guidance molecules as it migrates to its target; this sensitivity regulation is an important theme seen throughout development.

UNC is a set of proteins first identified through a set of screening tests in Caenorhabditis elegans, looking for roundworms with movement problems. Worms with which were un-coordinated were analysed in order to identify the genetic defect. Such proteins include UNC-5, a receptor for UNC-6 which is one of the netrins. Netrins are a class of proteins involved in axon guidance. UNC-5 uses repulsion (genetics) to direct axons while the other netrin receptor UNC-40 attracts axons to the source of netrin production.

UNC-5 is a receptor for netrins including UNC-6. Netrins are a class of proteins involved in axon guidance. UNC-5 uses repulsion to direct axons while the other netrin receptor UNC-40 attracts axons to the source of netrin production.

References

  1. ↑ "Wolpert, Lewis. Principles of Development: 3rd Edition. Oxford University Press, 2007."
  2. ↑ "Gilbert, Scott F. Principles of Development: 8th Edition. Sinauer Associates, Inc. 2006."
  3. ↑ "Jessell, Thomas M. Neuronal Specification in the spinal cord: inductive signals and transcriptional codes. Nature Reviews Genetics. Oct, 2000(1)"
  4. ↑ "Yamada, T. Control of Cell Pattern in the Developing Nervous System: Polarizing Activity of the Floor Plate and Notochord. Cell, Vol. 64, 635-647, February 8, 1991"
  5. ↑ "Strahle, Uwe, et al. Vertebrate floor-plate specification: variations on common themes. Trends in Genetics Vol.20 No.3 March 2004"
  6. ↑ "Patten, Iain, et al. Distinct modes of floor plate induction in the chick embryo. 19 June 2003. Development 130, 4809-4821"
  7. 1 2 "Guan KL and Rao Y. Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci. 2003 Dec;4(12):941-56."
  8. 1 2 "Serafini, Tito, et al. The Netrins Define a Family of Axon Outgrowth-Promoting Proteins Homologous to C. elegans UNC-6. Cell, Vol. 79, 409-424. August 12, 1994"
  9. ↑ "Kennedy, Timothy E, et al. Netrins Are Diffusible Chemotropic Factors for Commissural Axons in the Embryonic Spinal Cord. Cell, Vol. 79, 425-435, August 12, 1994"
  10. ↑ "Charron, F, et al. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell. 2003 Apr 4;113(1):11-23."
  11. ↑ Dominici, C; Moreno-Bravo, JA; Puiggros, SR; Rappeneau, Q; Rama, N; Vieugue, P; Bernet, A; Mehlen, P; Chédotal, A (18 May 2017). "Floor-plate-derived netrin-1 is dispensable for commissural axon guidance". Nature. 545 (7654): 350–354. doi:10.1038/nature22331. PMC   5438598 . PMID   28445456.
  12. ↑ "Long, Hua et al. Conserved Roles for Slit and Robo Proteins in Midline Commissural Axon Guidance. Neuron, Vol. 42, 213–223, April 22, 2004"
  13. ↑ Yu, Kwanha; McGlynn, Sean; Matise, Michael P. (2013-04-01). "Floor plate-derived sonic hedgehog regulates glial and ependymal cell fates in the developing spinal cord". Development. 140 (7): 1594–1604. doi:10.1242/dev.090845. ISSN   0950-1991. PMC   3596997 . PMID   23482494.
  14. ↑ Bai, C. Brian; Auerbach, Wojtek; Lee, Joon S.; Stephen, Daniel; Joyner, Alexandra L. (October 2002). "Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway". Development. 129 (20): 4753–4761. ISSN   0950-1991. PMID   12361967.
  15. ↑ Zou, Yimin (2015). "Wnt Signaling in Spinal Cord Injury". Wnt Signaling in Spinal Cord Injury - Neural Regeneration - Chapter 15. pp. 237–244. doi:10.1016/B978-0-12-801732-6.00015-X. ISBN   9780128017326.
  16. ↑ Abdulhaleem M, Felemban Athary; Song, Xiaohong; Kawano, Rie; Uezono, Naohiro; Ito, Ayako; Ahmed, Giasuddin; Hossain, Mahmud; Nakashima, Kinichi; Tanaka, Hideaki (2015-05-01). "Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord". Developmental Neurobiology. 75 (5): 494–504. doi:10.1002/dneu.22238. ISSN   1932-846X. PMID   25331329.
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