Neural development and regeneration: it's all in your spinal cord

Becker, Catherina G.; Corral, Ruth Díez del

doi:10.1242/dev.121053

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…However, cells described here in larvae differ from ERG cells because of the absence of expression of GFAP (Martinez‐De Luna et al, ) and GS. In addition, ERG cells have been proposed as the main source of progenitor cells for spinal cord repair (Becker & Diez del Corral, ). Based on this and the fact that type I, II, and III cells are present in the domains with the highest proliferative activity we propose that these cells are the most probable source of cells for repair.…”

Section: Discussionmentioning

confidence: 99%

Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis

Edwards-Faret¹,

Cebrián-Silla

Méndez-Olivos³

et al. 2018

J of Comparative Neurology

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Studying the cellular composition and morphological changes of cells lining the central canal during Xenopus laevis metamorphosis could contribute to understand postnatal development and spinal cord regeneration. Here we report the analysis of central canal cells at different stages during metamorphosis using immunofluorescence for protein markers expression, transmission and scanning electron microscopy and cell proliferation assays. The central canal was regionalized according to expression of glial markers, ultrastructure, and proliferation in dorsal, lateral, and ventral domains with differences between larvae and froglets. In regenerative larvae, all cell types were uniciliated, have a radial morphology, and elongated nuclei with lax chromatin, resembling radial glial cells. Important differences in cells of nonregenerative froglets were observed, although uniciliated cells were found, the most abundant cells had multicilia and revealed extensive changes in the maturation and differentiation state. The majority of dividing cells in larvae corresponded to uniciliated cells at dorsal and lateral domains in a cervical-lumbar gradient, correlating with undifferentiated features. Neurons contacting the lumen of the central canal were detected in both stages and revealed extensive changes in the maturation and differentiation state. However, in froglets a very low proportion of cells incorporate 5-ethynyl-2'-deoxyuridine (EdU), associated with the differentiated profile and with the increase of multiciliated cells. Our work showed progressive changes in the cell types lining the central canal of Xenopus laevis spinal cord which are correlated with the regenerative capacities.

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Section: Discussionmentioning

confidence: 99%

Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis

Edwards-Faret¹,

Cebrián-Silla

Méndez-Olivos³

et al. 2018

J of Comparative Neurology

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“…Studies on model systems such as mice, Drosophila etc., propose that neural patterning usually initiate with the specification on rostral-forebrain precursors (32,46) . The caudalising morphogens subsequently re-specify regional identity to establish other subdivisions of caudal neural precursors (47). Consistently, the rostral forebrain is also considered as a "default" cell fate during neural differentiation of hPSCs (19,22,23,48) .…”

Section: Disscussionmentioning

confidence: 96%

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition

Zhang

Liao

et al. 2018

Journal of Biological Chemistry

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During neurogenesis, neural patterning is a critical step during which neural progenitor cells (NPCs) differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here, we optimized the "dual-SMAD inhibition" method to specifically promote differentiation of human pluripotent stem cells (hPSCs) into forebrain and hindbrain NPCs along the rostral-caudal (R-C) axes. We report that neural patterning determination occurs at the very early stage in this differentiation. Undifferentiated hPSCs expressed basal levels of the transcription factor orthodenticle homeobox 2 (OTX2) that dominantly drove hPSCs into the "default" rostral fate at the beginning of differentiation. Inhibition of glycogen synthase kinase 3β (GSK3β) through CHIR99021 (CHIR) application sustained transient expression of the transcription factor NANOG at early differentiation stages through Wnt signaling. Wnt signaling and NANOG antagonized OTX2 and in the later stages of differentiation, switched the default rostral cell fate to the caudal one. Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans.The embryonic neurodevelopment is a spatiotemporally regulated process, during which http://www.jbc.org/ Downloaded from 2 distinct cell fates are progressively restricted based on spatial regions (1, 2). At early stage of neurogenesis, the specified neural ectoderm divides into functionally distinct cell fates along the anterior-posterior (A-P) and dorsal-ventral (D-V) axes (3). This neural patterning process is a critical step to specify different neural precursors such as forebrain, midbrain, hindbrain and spinal cord. It has been known that the neural patterning is induced by the temporal and special morphogen gradients along the A-P and D-V axes (4, 5). These morphogens, including BMPs, WNTs, FGFs, RA and SHH (sonic hedgehog), coordinate and form gradients to specify regionally transcriptional program and distinct neural progenitors (6-10). However, the precise timing and mechanisms underlying morphogeninduced neuraxial patterning has not been fully elucidated in mammals, especially in human.Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC) could differentiate into neuroepithelial cells , regionally specified neural precursor cells (11-16), thus provides a valuable model to investigate molecular determinants on neural patterning in human background. The mostly used method to induce neural differentiation in hPSCs is through suppression of both TGFβ and BMP signaling (17,18). Dual-inhibition of SMAD-dependent TGF-β and BMP signaling by their inhibitors (SB431542 and Noggin), or SB431542 and Dorsomorphin can efficiently trigger hPSCs differentiation into NPCs (19-21). Dual-SMAD inhibition triggered NPCs are believed to be more close to the anterior forebrai...

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“…The radial morphology and expression of astrocyte markers makes these cells similar to radial glia, progenitor cells in the CNS of developing mammals ( Examples (in red) shown are epimorphic regeneration of the entire spinal cord in salamanders, interstitial regeneration of neurons in an area surrounding a stab lesion of the telencephalon or spinal cord transection in zebrafish, and regeneration of specifc cell types; e.g., dopaminergic neurons in the midbrain of salamanders after toxin-mediated ablation. The retina of fishes and salamanders is also capable of epimorphic and interstitial regeneration after these types of injury, which is comprehensively reviewed elsewhere (Goldman, 2014;Gorsuch and Hyde, 2014;Lenkowski and Raymond, 2014 Review also have clear ependymal features; e.g., in the zebrafish spinal cord they contribute to the ependyma and may possess motile cilia (L. Saude, personal communication; see Becker and Diez del Corral, 2015). We therefore designated these cells in adult anamniotes ''ependymo-radial glia (ERG)'' (Reimer et al, 2008).…”

Section: Types and Extent Of Neuronal Regeneration In The Cns Of Anammentioning

confidence: 99%

Neuronal Regeneration from Ependymo-Radial Glial Cells: Cook, Little Pot, Cook!

Becker

2015

Developmental Cell

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Adult fish and salamanders regenerate specific neurons as well as entire CNS areas after injury. Recent studies shed light on how these anamniotes activate progenitor cells, generate the required cell types, and functionally integrate these into a complex environment. Some developmental signals and mechanisms are recapitulated during neuronal regeneration, whereas others are unique to the regeneration process. The use of genetic techniques, such as cell ablation and lineage-tracing, in combination with cell-type-specific expression profiling reveal factors that initiate, fine-tune, and terminate the regenerative response in anamniotes, with a view to translating findings to non-regenerating species.

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Neural development and regeneration: it's all in your spinal cord

Cited by 15 publications

References 29 publications

Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis

Cellular composition and organization of the spinal cord central canal during metamorphosis of the frog Xenopus laevis

Antagonism between the transcription factors NANOG and OTX2 specifies rostral or caudal cell fate during neural patterning transition

Neuronal Regeneration from Ependymo-Radial Glial Cells: Cook, Little Pot, Cook!

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