A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification

Bennett G. Novitch; Hynek Wichterle; Thomas M. Jessell; Shanthini Sockanathan

doi:10.1016/j.neuron.2003.08.006

A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification

Bennett G. Novitch, Hynek Wichterle, Thomas M. Jessell, Shanthini Sockanathan

School of Medicine

Research output: Contribution to journal › Article › peer-review

249 Scopus citations

Abstract

The specification of neuronal fates in the ventral spinal cord depends on the regulation of homeodomain (HD) and basic-helix-loop-helix (bHLH) proteins by Sonic hedgehog (Shh). Most of these transcription factors function as repressors, leaving unresolved the link between inductive signaling pathways and transcriptional activators involved in ventral neuronal specification. We show here that retinoid signaling and the activator functions of retinoid receptors are required to pattern the expression of HD and bHLH proteins and to specify motor neuron identity. We also show that fibroblast growth factors (FGFs) repress progenitor HD protein expression, implying that evasion of FGF signaling and exposure to retinoid and Shh signals are obligate steps in the emergence of ventral neural pattern. Moreover, joint exposure of neural progenitors to retinoids and FGFs suffices to induce motor neuron differentiation in a Shh-independent manner.

Original language	English (US)
Pages (from-to)	81-95
Number of pages	15
Journal	Neuron
Volume	40
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2003.08.006
State	Published - Sep 25 2003

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2003.08.006

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title = "A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification",

abstract = "The specification of neuronal fates in the ventral spinal cord depends on the regulation of homeodomain (HD) and basic-helix-loop-helix (bHLH) proteins by Sonic hedgehog (Shh). Most of these transcription factors function as repressors, leaving unresolved the link between inductive signaling pathways and transcriptional activators involved in ventral neuronal specification. We show here that retinoid signaling and the activator functions of retinoid receptors are required to pattern the expression of HD and bHLH proteins and to specify motor neuron identity. We also show that fibroblast growth factors (FGFs) repress progenitor HD protein expression, implying that evasion of FGF signaling and exposure to retinoid and Shh signals are obligate steps in the emergence of ventral neural pattern. Moreover, joint exposure of neural progenitors to retinoids and FGFs suffices to induce motor neuron differentiation in a Shh-independent manner.",

author = "Novitch, {Bennett G.} and Hynek Wichterle and Jessell, {Thomas M.} and Shanthini Sockanathan",

note = "Funding Information: We thank Thomas Perlmann and Sara Wilson for reagents and James Briscoe, Jeremy Dasen, Johan Ericson, and Sara Wilson for comments on the manuscript. We are grateful to Susan Kales and Qiaolian Liu for technical assistance and to Kathy MacArthur for help in preparing the manuscript. We thank Curis, Inc., for generously providing the Hh agonist Hh-Ag1.3. We also thank Kate Storey for discussions before submission of the manuscript. B.G.N. was supported as a Marion Abbe Fellow of the Damon Runyon Cancer Research Fund, DRG-1569. H.W. was supported by Damon Runyon Cancer Research Fund, DRG-1683. S.S. was supported by grants from the Whitehall Foundation and the Muscular Dystrophy Association. T.M.J. was supported by grants from NINDS and Project ALS and is an HHMI Investigator.",

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N1 - Funding Information: We thank Thomas Perlmann and Sara Wilson for reagents and James Briscoe, Jeremy Dasen, Johan Ericson, and Sara Wilson for comments on the manuscript. We are grateful to Susan Kales and Qiaolian Liu for technical assistance and to Kathy MacArthur for help in preparing the manuscript. We thank Curis, Inc., for generously providing the Hh agonist Hh-Ag1.3. We also thank Kate Storey for discussions before submission of the manuscript. B.G.N. was supported as a Marion Abbe Fellow of the Damon Runyon Cancer Research Fund, DRG-1569. H.W. was supported by Damon Runyon Cancer Research Fund, DRG-1683. S.S. was supported by grants from the Whitehall Foundation and the Muscular Dystrophy Association. T.M.J. was supported by grants from NINDS and Project ALS and is an HHMI Investigator.

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A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification

Abstract

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