Onecut factors and Pou2f2 regulate the distribution of V2 interneurons in the mouse developing spinal cord

AbstractAcquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.Significance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

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ISDN2012_0184: The Onecut transcription factors participate in the differentiation and migration of distinct subsets of ventral interneurons in the developing spinal cord

International Journal of Developmental Neuroscience ◽

10.1016/j.ijdevneu.2012.10.012 ◽

2012 ◽

Vol 30 (8) ◽

pp. 673-673

Author(s):

C. Francius ◽

A. Harris ◽

T. Hendricks ◽

M. Goulding. ◽

F. Clotman

Keyword(s):

Spinal Cord ◽

Transcription Factors ◽

And Migration ◽

Developing Spinal Cord

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Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Science Advances ◽

10.1126/sciadv.abg5968 ◽

2021 ◽

Vol 7 (24) ◽

pp. eabg5968

Author(s):

Baruch Haimson ◽

Oren Meir ◽

Reut Sudakevitz-Merzbach ◽

Gerard Elberg ◽

Samantha Friedrich ◽

...

Keyword(s):

Spinal Cord ◽

Mutant Mouse ◽

Loss Of Function ◽

Dorsal Midline ◽

Roof Plate ◽

Embryonic Spinal Cord ◽

Guidance Molecule

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression and is missing in galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. Dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.

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Anteroposterior Wnt-RA Gradient Defines Adhesion and Migration Properties of Neural Progenitors in Developing Spinal Cord

Stem Cell Reports ◽

10.1016/j.stemcr.2020.08.016 ◽

2020 ◽

Vol 15 (4) ◽

pp. 898-911

Author(s):

Mohammed R. Shaker ◽

Ju-Hyun Lee ◽

Si-Hyung Park ◽

Joo Yeon Kim ◽

Gi Hoon Son ◽

...

Keyword(s):

Spinal Cord ◽

Neural Progenitors ◽

And Migration ◽

Developing Spinal Cord

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Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord

Development ◽

10.1242/dev.001255 ◽

2007 ◽

Vol 134 (8) ◽

pp. 1617-1629 ◽

Cited By ~ 127

Author(s):

M. Sugimori ◽

M. Nagao ◽

N. Bertrand ◽

C. M. Parras ◽

F. Guillemot ◽

...

Keyword(s):

Spinal Cord ◽

Transcription Factors ◽

Hlh Transcription Factors ◽

Spatiotemporal Control ◽

Developing Spinal Cord

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HoxD transcription factors define monosynaptic sensory-motor specificity in the developing spinal cord

Development ◽

10.1242/dev.191122 ◽

2021 ◽

Author(s):

Fumiyasu Imai ◽

Mike Adam ◽

S. Steven Potter ◽

Yutaka Yoshida

Keyword(s):

Spinal Cord ◽

Transcription Factors ◽

Motor Neuron ◽

Sensory Neurons ◽

Motor Neurons ◽

Critical Role ◽

Dendrite Morphology ◽

Sensory Motor ◽

Integral Role ◽

Developing Spinal Cord

The specificity of monosynaptic connections between proprioceptive sensory neurons and their recipient spinal motor neurons depends on multiple factors, including motor neuron positioning and dendrite morphology, axon projection patterns of proprioceptive sensory neurons in the spinal cord, and the ligand-receptor molecules involved in cell-to-cell recognition. However, with few exceptions, the transcription factors engaged in this process are poorly characterized. We show here, that members of the HoxD family of transcription factors play a critical role in the specificity of monosynaptic sensory-motor connections. Mice lacking Hoxd9, Hoxd10, and Hoxd11 exhibit defects in locomotion but have no obvious defects in motor neuron positioning or dendrite morphology through the medio-lateral and rostro-caudal axes. However, we found that quadriceps motor neurons in these mice show aberrant axon development and receive inappropriate inputs from proprioceptive sensory axons innervating the obturator muscle. These genetic studies demonstrate that the HoxD transcription factors play an integral role in the synaptic specificity of monosynaptic sensory-motor connections in the developing spinal cord.

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HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1

Development ◽

10.1242/dev.195404 ◽

2021 ◽

Vol 148 (4) ◽

pp. dev195404

Author(s):

Axelle Wilmerding ◽

Lucrezia Rinaldi ◽

Nathalie Caruso ◽

Laure Lo Re ◽

Emilie Bonzom ◽

...

Keyword(s):

Spinal Cord ◽

Neural Tube ◽

Leucine Zipper ◽

Hox Genes ◽

Neuronal Diversity ◽

Loss Of Function ◽

Mantle Zone ◽

Hox Proteins ◽

Additional Function ◽

Developing Spinal Cord

ABSTRACTDifferential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ). Gain-of-function experiments of HoxB4, HoxB8 and HoxB9, respectively, representative of anterior, central and posterior HoxB genes, resulted in ectopic progenitor cells in the mantle zone. The search for HoxB8 downstream targets in the early neural tube identified the leucine zipper tumor suppressor 1 gene (Lzts1), the expression of which is also activated by HoxB4 and HoxB9. Gain- and loss-of-function experiments showed that Lzts1, which is expressed endogenously in the IZ, controls neuronal delamination. These data collectively indicate that HoxB genes have a generic function in the developing spinal cord, controlling the expression of Lzts1 and neuronal delamination.

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Ependymal morphogenesis in a simple vertebrate spinal cord

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147958 ◽

1993 ◽

Vol 51 ◽

pp. 424-425

Author(s):

Jill K. Frey ◽

Aileen Chen ◽

R. David Heathcote

Keyword(s):

Spinal Cord ◽

Cerebrospinal Fluid ◽

Single Layer ◽

Central Canal ◽

Floor Plate ◽

Turn Of The Century ◽

Ependymal Cells ◽

Embryonic Spinal Cord ◽

Developing Spinal Cord ◽

Tyrosine Hydroxylase Immunocytochemistry

All cells of the spinal cord originate from the single layer of neuroepithelium that lines the central canal. Since the turn of the century, it has been known that a subclass of these ependymal cells can differentiate into neurons and extend cytoplasmic projections and cilia into the central canal. We have recently used tyrosine hydroxylase immunocytochemistry to identify a catecholaminergic subpopulation of cerebrospinal fluid (CSF) contacting ependymal neurons in the developing spinal cord of the frog Xenopus laevis (Fig. 1). The interneurons are located in the floor plate region of the spinal cord and have axons that extend rostrally toward the hindbrain. During the morphogenesis of the catecholaminergic population of cells, two longitudinal columns gradually appear and then rapidly “converge” at the ventral midline. Transverse sections of embryonic spinal cord (see Fig. 1) showed that the cell bodies decreased in size and underwent changes in shape, number and position within the spinal cord.

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