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Published January 1, 2018 | Supplemental Material + Accepted Version
Journal Article Open

Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells

Abstract

The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo.

Additional Information

© 2017 Elsevier Inc. Received 10 October 2017, Accepted 23 October 2017, Available online 3 November 2017. We thank Kenneth Poss, Stephanie Woo and Iain Shepherd for fish lines, the Zebrafish International Resource Center (ZIRC) for cDNA constructs, David Tobin for the pME-Turquoise construct. We thank Yuwei Li for help with cell track analysis, Can Li, Wael El-Nachef, Kendrick Shen and Joanne Tan-Cabugao for technical assistance and David Mayorga for fish care. Confocal imaging and Imaris image analysis for this study was performed in the Biological Imaging Facility (BIF), Caltech. This work was funded by a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award (PDEP) and a NIH National Research Service Award (NRSA) HD080343 to R.A.U.; by a Caltech Summer Undergraduate Research Fellowship (SURF) to S.S.H; by a NIH grant DE024157 and a fish facility grant from Beckman Institute, Caltech, to M.E.B. The authors declare no competing financial interests. Author Contributions: R.A.U. and M.E.B designed the study; R.A.U. and S.S.H. performed experiments and collected data; R.A.U. and M.E.B. analyzed data, drafted the manuscript and obtained funding.

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Created:
August 21, 2023
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October 17, 2023