SMN participates in the positioning of motor neurons in the ventral neural tube

Neurotrophins signal through members of the trk family of tyrosine kinase receptors and are known to regulate several neuronal properties. Although initially characterized by their ability to prevent naturally occurring cell death of subsets of neurons during development, neurotrophins can also regulate the proliferation and differentiation of precursor cells. Here we report a novel involvement of neurotrophins in early development of the neural tube. We demonstrate that a functional trkB receptor is expressed by motor neuron progenitors in the ventral neural tube and that treatment of ventral neural tube explants with the trkB ligand Brain-Derived Neurotrophic Factor (BDNF) leads to a significant increase in the number of motor neurons. The only BDNF expression detectable at this stage is by a subset of ventrally projecting interneurons in the dorsal neural tube; ablating this region in vivo leads to a reduction of motor neuron numbers. This loss can be prevented by simultaneous treatment with BDNF. We propose that BDNF produced by dorsal interneurons stimulates proliferation and/or differentiation of motor neuron progenitors after anterograde axonal transport and release in proximity to the trkB-expressing motor neuron precursors, thereby coordinating development between dorsal and ventral regions of the neural tube.

Download Full-text

SMN: A role in axon growth/fasciculation and retaining MMC(m) motor neurons in the ventral neural tube

Developmental Biology ◽

10.1016/j.ydbio.2011.05.278 ◽

2011 ◽

Vol 356 (1) ◽

pp. 199-200

Author(s):

Catherine E. Krull ◽

Fengyun Su ◽

Mustafa Sahin

Keyword(s):

Motor Neurons ◽

Neural Tube ◽

Axon Growth ◽

Ventral Neural Tube

Download Full-text

Slit/Robo signals prevent spinal motor neuron emigration by organizing the spinal cord basement membrane

10.1101/690859 ◽

2019 ◽

Author(s):

Minkyung Kim ◽

Clare H Lee ◽

Sarah J Barnum ◽

Roland CJ Watson ◽

Jennifer Li ◽

...

Keyword(s):

Spinal Cord ◽

Basement Membrane ◽

Motor Neuron ◽

Motor Neurons ◽

Neural Tube ◽

Spinal Motor Neuron ◽

Spinal Motor Neurons ◽

Spinal Motor ◽

Ventral Neural Tube ◽

Set Up

AbstractThe developing spinal cord builds a boundary between the CNS and the periphery, in the form of a basement membrane. The spinal cord basement membrane is a barrier that retains CNS neuron cell bodies, while being selectively permeable to specific axon types. Spinal motor neuron cell bodies are located in the ventral neural tube next to the floor plate and project their axons out through the basement membrane to peripheral targets. However, little is known about how spinal motor neuron cell bodies are retained inside the ventral neural tube, while their axons can exit. In previous work, we found that disruption of Slit/Robo signals caused motor neuron emigration outside the spinal cord. In the current study, we investigate how Slit/Robo signals are necessary to keep spinal motor neurons within the neural tube. Our findings show that when Slit/Robo signals were removed from motor neurons, they migrated outside the spinal cord. Furthermore, this emigration was associated with abnormal basement membrane protein expression in the ventral spinal cord. Using Robo2 and Slit2 conditional mutants, we found that motor neuron-derived Slit/Robo signals were required to set up a normal basement membrane in the spinal cord. Together, our results suggest that motor neurons produce Slit signals that are required for the basement membrane assembly to retain motor neuron cell bodies within the spinal cord.

Download Full-text

Retinoid-binding protein distribution in the developing mammalian nervous system

Development ◽

10.1242/dev.109.1.75 ◽

1990 ◽

Vol 109 (1) ◽

pp. 75-80 ◽

Cited By ~ 3

Author(s):

M. Maden ◽

D.E. Ong ◽

F. Chytil

Keyword(s):

Nervous System ◽

Retinoic Acid ◽

Neural Crest ◽

Motor Neurons ◽

Neural Tube ◽

Binding Protein ◽

Sympathetic Ganglia ◽

Retinol Binding Protein ◽

Otic Vesicle ◽

Protein Distribution

We have analysed the distribution of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the day 8.5-day 12 mouse and rat embryo. CRBP is localised in the heart, gut epithelium, notochord, otic vesicle, sympathetic ganglia, lamina terminalis of the brain, and, most strikingly, in a ventral stripe across the developing neural tube in the future motor neuron region. This immunoreactivity remains in motor neurons and, at later stages, motor axons are labelled in contrast to unlabelled sensory axons. CRABP is localised to the neural crest cells, which are particularly noticeable streaming into the branchial arches. At later stages, neural crest derivatives such as Schwann cells, cells in the gut wall and sympathetic ganglia are immunoreactive. An additional area of CRABP-positive cells are neuroblasts in the mantle layer of the neural tube, which subsequently appear to be the axons and cell bodies of the commissural system. Since retinol and retinoic acid are the endogenous ligands for these binding proteins, we propose that retinoids may play a role in the development and differentiation of the mammalian nervous system and may interact with certain homoeobox genes whose transcripts have also been localised within the nervous system.

Download Full-text

Sonic hedgehog synergizes with the extracellular matrix protein vitronectin to induce spinal motor neuron differentiation

Development ◽

10.1242/dev.127.2.333 ◽

2000 ◽

Vol 127 (2) ◽

pp. 333-342 ◽

Cited By ~ 6

Author(s):

S. Pons ◽

E. Marti

Keyword(s):

Extracellular Matrix ◽

Motor Neuron ◽

Sonic Hedgehog ◽

Motor Neurons ◽

Neural Tube ◽

Matrix Protein ◽

Floor Plate ◽

Binding Domain ◽

Extracellular Matrix Protein ◽

Neuron Differentiation

Patterning of the vertebrate neural tube depends on intercellular signals emanating from sources such as the notochord and the floor plate. The secreted protein Sonic hedgehog and the extracellular matrix protein Vitronectin are both expressed in these signalling centres and have both been implicated in the generation of ventral neurons. The proteolytic processing of Sonic hedgehog is fundamental for its signalling properties. This processing generates two secreted peptides with all the inducing activity of Shh residing in the highly conserved 19 kDa amino-terminal peptide (N-Shh). Here we show that Vitronectin is also proteolitically processed in the embryonic chick notochord, floor plate and ventral neural tube and that this processing is spatiotemporally correlated with the generation of motor neurons. The processing of Vitronectin produces two fragments of 54 kDa and 45 kDa, as previously described for Vitronectin isolated from chick yolk. The 45 kDa fragment lacks the heparin-binding domain and the integrin-binding domain, RGD, present in the non-processed Vitronectin glycoprotein. Here we show that N-Shh binds to the three forms of Vitronectin (70, 54 and 45 kDa) isolated from embryonic tissue, although is preferentially associated with the 45 kDa form. Furthermore, in cultures of dissociated neuroepithelial cells, the combined addition of N-Shh and Vitronectin significantly increases the extent of motor neuron differentiation, as compared to the low or absent inducing capabilities of either N-Shh or Vitronectin alone. Thus, we conclude that the differentiation of motor neurons is enhanced by the synergistic action of N-Shh and Vitronectin, and that Vitronectin may be necessary for the proper presentation of the morphogen N-Shh to one of its target cells, the differentiating motor neurons.

Download Full-text

Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1

Development ◽

10.1242/dev.121.11.3675 ◽

1995 ◽

Vol 121 (11) ◽

pp. 3675-3686 ◽

Cited By ~ 40

Author(s):

H.M. Stern ◽

A.M. Brown ◽

S.D. Hauschka

Keyword(s):

Neural Tube ◽

Muscle Development ◽

Paraxial Mesoderm ◽

Myogenic Response ◽

Dorsal Neural Tube ◽

Ventral Neural Tube ◽

Myogenic Induction ◽

Inductive Activity

Previous studies have demonstrated that the neural tube/notochord complex is required for skeletal muscle development within somites. In order to explore the localization of myogenic inducing signals within the neural tube, dorsal or ventral neural tube halves were cultured in contact with single somites or pieces of segmental plate mesoderm. Somites and segmental plates cultured with the dorsal half of the neural tube exhibited 70% and 85% myogenic response rates, as determined by immunostaining for myosin heavy chain. This response was slightly lower than the 100% response to whole neural tube/notochord, but was much greater than the 30% and 10% myogenic response to ventral neural tube with and without notochord. These results demonstrate that the dorsal neural tube emits a potent myogenic inducing signal which accounts for most of the inductive activity of whole neural tube/notochord. However, a role for ventral neural tube/notochord in somite myogenic induction was clearly evident from the larger number of myogenic cells induced when both dorsal neural tube and ventral neural tube/notochord were present. To address the role of a specific dorsal neural tube factor in somite myogenic induction, we tested the ability of Wnt-1-expressing fibroblasts to promote paraxial mesoderm myogenesis in vitro. We found that cells expressing Wnt-1 induced a small number of somite and segmental plate cells to undergo myogenesis. This finding is consistent with the localized dorsal neural tube inductive activity described above, but since the ventral neural tube/notochord also possesses myogenic inductive capacity yet does not express Wnt-1, additional inductive factors are likely involved.

Download Full-text

Cell-autonomous shift from axial to paraxial mesodermal development in zebrafish floating head mutants

Development ◽

10.1242/dev.121.12.4257 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4257-4264 ◽

Cited By ~ 25

Author(s):

M.E. Halpern ◽

C. Thisse ◽

R.K. Ho ◽

B. Thisse ◽

B. Riggleman ◽

...

Keyword(s):

Neural Tube ◽

Single Cells ◽

Floor Plate ◽

Paraxial Mesoderm ◽

Wild Type ◽

Genetic Mosaics ◽

Essential Step ◽

Ventral Neural Tube ◽

Mesodermal Development

Zebrafish floating head mutant embryos lack notochord and develop somitic muscle in its place. This may result from incorrect specification of the notochord domain at gastrulation, or from respecification of notochord progenitors to form muscle. In genetic mosaics, floating head acts cell autonomously. Transplanted wild-type cells differentiate into notochord in mutant hosts; however, cells from floating head mutant donors produce muscle rather than notochord in wild-type hosts. Consistent with respecification, markers of axial mesoderm are initially expressed in floating head mutant gastrulas, but expression does not persist. Axial cells also inappropriately express markers of paraxial mesoderm. Thus, single cells in the mutant midline transiently co-express genes that are normally specific to either axial or paraxial mesoderm. Since floating head mutants produce some floor plate in the ventral neural tube, midline mesoderm may also retain early signaling capabilities. Our results suggest that wild-type floating head provides an essential step in maintaining, rather than initiating, development of notochord-forming axial mesoderm.

Download Full-text

Single cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human specific features

10.1101/2021.04.12.439474 ◽

2021 ◽

Author(s):

Teresa Rayon ◽

Rory J. Maizels ◽

Christopher Barrington ◽

James Briscoe

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Single Cell ◽

Motor Neurons ◽

Neural Tube ◽

Transcriptome Profiling ◽

Cell Types ◽

Human Embryos ◽

Neuronal Populations ◽

Cell Transcriptome

AbstractThe spinal cord receives input from peripheral sensory neurons and controls motor output by regulating muscle innervating motor neurons. These functions are carried out by neural circuits comprising molecularly and physiologically distinct neuronal subtypes that are generated in a characteristic spatial-temporal arrangement from progenitors in the embryonic neural tube. The systematic mapping of gene expression in mouse embryos has provided insight into the diversity and complexity of cells in the neural tube. For human embryos, however, less information has been available. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions in four human embryos of Carnegie Stages (CS) CS12, CS14, CS17 and CS19 from Gestational Weeks (W) 4-7. In total we recovered the transcriptomes of 71,219 cells. Analysis of progenitor and neuronal populations from the neural tube, as well as cells of the peripheral nervous system, in dorsal root ganglia adjacent to the neural tube, identified dozens of distinct cell types and facilitated the reconstruction of the differentiation pathways of specific neuronal subtypes. Comparison with existing mouse datasets revealed the overall similarity of mouse and human neural tube development while highlighting specific features that differed between species. These data provide a catalogue of gene expression and cell type identity in the developing neural tube that will support future studies of sensory and motor control systems and can be explored at https://shiny.crick.ac.uk/scviewer/neuraltube/.

Download Full-text

The zebrafish T-box genesno tailandspadetailare required for development of trunk and tail mesoderm and medial floor plate

Development ◽

10.1242/dev.129.14.3311 ◽

2002 ◽

Vol 129 (14) ◽

pp. 3311-3323 ◽

Cited By ~ 6

Author(s):

Sharon L. Amacher ◽

Bruce W. Draper ◽

Brian R. Summers ◽

Charles B. Kimmel

Keyword(s):

Embryonic Development ◽

Neural Tube ◽

Transcriptional Regulators ◽

Floor Plate ◽

Wild Type ◽

T Box ◽

No Tail ◽

Ventral Neural Tube ◽

Plate Formation ◽

In Cells

T-box genes encode transcriptional regulators that control many aspects of embryonic development. Here, we demonstrate that the mesodermally expressed zebrafish spadetail (spt)/VegT and no tail (ntl)/Brachyury T-box genes are semi-redundantly and cell-autonomously required for formation of all trunk and tail mesoderm. Despite the lack of posterior mesoderm in spt–;ntl– embryos, dorsal-ventral neural tube patterning is relatively normal, with the notable exception that posterior medial floor plate is completely absent. This contrasts sharply with observations in single mutants, as mutations singly in ntl or spt enhance posterior medial floor plate development. We find that ntl function is required to repress medial floor plate and promote notochord fate in cells of the wild-type notochord domain and that spt and ntl together are required non cell-autonomously for medial floor plate formation, suggesting that an inducing signal present in wild-type mesoderm is lacking in spt–;ntl– embryos.

Download Full-text