Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

SummaryDuring early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

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FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord

10.1101/690263 ◽

2019 ◽

Author(s):

Abdulmajeed Fahad Alrefaei ◽

Andrea E. Münsterberg ◽

Grant N. Wheeler

Keyword(s):

Spinal Cord ◽

Cell Proliferation ◽

Neural Tube ◽

Spinal Cord Development ◽

Dorsal Neural Tube ◽

Wnt Ligands ◽

Frizzled Receptors ◽

Developmental Contexts ◽

Developing Spinal Cord

AbstractWnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β-catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.

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Genetically identified spinal interneurons integrating tactile afferents for motor control

Journal of Neurophysiology ◽

10.1152/jn.00522.2015 ◽

2015 ◽

Vol 114 (6) ◽

pp. 3050-3063 ◽

Cited By ~ 5

Author(s):

Tuan V. Bui ◽

Nicolas Stifani ◽

Izabela Panek ◽

Carl Farah

Keyword(s):

Spinal Cord ◽

Motor Control ◽

Sensory Information ◽

Spinal Neuron ◽

Spinal Neurons ◽

Tactile Information ◽

Spinal Interneurons ◽

Motor Circuits ◽

Neuron Populations ◽

Genetic Techniques

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing.

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Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

eLife ◽

10.7554/elife.55665 ◽

2021 ◽

Vol 10 ◽

Author(s):

Emanuel Cura Costa ◽

Leo Otsuki ◽

Aida Rodrigo Albors ◽

Elly M Tanaka ◽

Osvaldo Chara

Keyword(s):

Cell Cycle ◽

Spinal Cord ◽

Spinal Cord Injuries ◽

Ependymal Cells ◽

Spatiotemporal Pattern ◽

Spinal Cord Regeneration ◽

Proliferation Zone ◽

Appearance Time ◽

Bona Fide

Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modelling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830mm of the injury. We adapted FUCCI technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.

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The developmental hourglass model is applicable to the spinal cord

10.1101/2021.03.08.434342 ◽

2021 ◽

Author(s):

Katsuki Mukaigasa ◽

Chie Sakuma ◽

Hiroyuki Yaginuma

Keyword(s):

Spinal Cord ◽

Regulatory Elements ◽

Spinal Neurons ◽

Upstream Gene ◽

Spinal Cord Development ◽

Neuronal Progenitor ◽

Before And After ◽

Hourglass Model ◽

Fate Determinants ◽

Developmental Hourglass

SummaryThe developmental hourglass model predict that embryonic morphology is most conserved at mid-embryonic stage and diverge at early and late stage. This model is generally considered by whole embryonic level. Here, we demonstrate that the hourglass model is also applicable to the more reduced element, the spinal cord. In the middle of the spinal cord development, dorsoventrally arrayed neuronal progenitor domains are established, which is conserved among vertebrates. We found that, by comparing the single-cell transcriptomes between mice and zebrafish, V3 interneurons, a subpopulation of the post-mitotic spinal neurons, display the divergent molecular profiles. We also found non-conservation of cis-regulatory elements located around the progenitor fate determinants, indicating the rewiring of the upstream gene regulatory network. These results demonstrate that, despite the conservation of the progenitor domains, processes before and after the progenitor domain specification has diverged. This study may help understand the molecular basis of the developmental hourglass model.

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Evolution of lbx spinal cord expression and function

10.1101/2020.12.30.424885 ◽

2020 ◽

Author(s):

José L. Juárez-Morales ◽

Frida Weierud ◽

Samantha England ◽

Celia Denby ◽

Nicole Santos ◽

...

Keyword(s):

Spinal Cord ◽

System Development ◽

Expression Patterns ◽

Cell Types ◽

Nervous System Development ◽

Spinal Neuron ◽

Neuron Development ◽

Spinal Neurons ◽

Excitatory Neurons ◽

And Function

AbstractLadybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many different animals. Amniotes have two Lbx genes, Lbx1 and Lbx2, but only Lbx1 is expressed in the spinal cord. In contrast, teleosts have three lbx genes, lbx1a, lbx1b and lbx2. In this study, we characterize the spinal cord expression of zebrafish lbx1a, lbx1b and lbx2 and show that each of these genes is expressed by distinct cell types. Our data suggest that lbx1a is expressed by dI4, dI5 and dI6 spinal interneurons, whereas lbx1b and lbx2 are primarily expressed in different spinal cord progenitor domains. We investigated the evolution of Lbx spinal cord expression patterns by examining Lbx1 and Lbx2 expression in the lesser spotted dogfish, Scyliorhinus canicula and Lbx1 expression in the tetrapod, Xenopus tropicalis. Our results suggest that zebrafish lbx1a spinal cord expression is conserved with that of Lbx1 in other vertebrates, whereas lbx1b spinal cord expression probably evolved in teleosts after the duplication of lbx1 into lbx1a and lbx1b. lbx2 spinal expression was probably acquired somewhere in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. Consistent with its conserved spinal cord expression pattern, we also show that the spinal cord function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction of inhibitory spinal neurons and an increase in excitatory neurons, similar to the phenotype of mouse Lbx1 mutants. Interestingly, we also see a reduction of inhibitory spinal neurons in lbx1b mutants, although in this case there is not a corresponding increase in the number of excitatory neurons and lbx1a;lbx1b double mutants do not have a more severe spinal cord phenotype than lbx1a single mutants, suggesting that lbx1a and lbx1b do not act redundantly in spinal neuron development. This suggests that lbx1b and lbx1a may be required in succession for correct specification of inhibitory dI4 and dI6 interneurons, although only lbx1a is required for suppression of excitatory fates in these cells.

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An Early Developmental Marker for Radial Glia in Rat Spinal Cord

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162648 ◽

1996 ◽

Vol 54 ◽

pp. 36-37

Author(s):

V. Kriho ◽

H.-Y. Yang ◽

C.-M. Lue ◽

N. Lieska ◽

G. D. Pappas

Keyword(s):

Spinal Cord ◽

Intermediate Filament ◽

Radial Glia ◽

Rat Spinal Cord ◽

Future Studies ◽

Spinal Cord Development ◽

Median Septum ◽

Differentiation Marker ◽

Early Developmental ◽

Developing Rat

Radial glia have been classically defined as those early glial cells that radially span their thin processes from the ventricular to the pial surfaces in the developing central nervous system. These radial glia constitute a transient cell population, disappearing, for the most part, by the end of the period of neuronal migration. Traditionally, it has been difficult to definitively identify these cells because the principal criteria available were morphologic only.Using immunofluorescence microscopy, we have previously defined a phenotype for radial glia in rat spinal cord based upon the sequential expression of vimentin, glial fibrillary acidic protein and an intermediate filament-associated protein, IFAP-70/280kD. We report here the application of another intermediate filament-associated protein, IFAP-300kD, originally identified in BHK-21 cells, to the immunofluorescence study of radial glia in the developing rat spinal cord.Results showed that IFAP-300kD appeared very early in rat spinal cord development. In fact by embryonic day 13, IFAP-300kD immunoreactivity was already at its peak and was observed in most of the radial glia which span the spinal cord from the ventricular to the subpial surfaces (Fig. 1). Interestingly, from this time, IFAP-300kD immunoreactivity diminished rapidly in a dorsal to ventral manner, so that by embryonic day 16 it was detectable only in the maturing macroglial cells in the marginal zone of the spinal cord and the dorsal median septum (Fig. 2). By birth, the spinal cord was essentially immuno-negative for this IFAP. Thus, IFAP-300kD appears to be another differentiation marker available for future studies of gliogenesis, especially for the early stages of radial glia differentiation.

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