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Published November 1, 2015 | Published + Supplemental Material
Journal Article Open

Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development

Abstract

During development, vagal neural crest cells fated to contribute to the enteric nervous system migrate ventrally away from the neural tube toward and along the primitive gut. The molecular mechanisms that regulate their early migration en route to and entry into the gut remain elusive. Here, we show that the transcription factor meis3 is expressed along vagal neural crest pathways. Meis3 loss of function results in a reduction in migration efficiency, cell number and the mitotic activity of neural crest cells in the vicinity of the gut, while having no effect on neural crest or gut specification. Later, during enteric nervous system differentiation, Meis3 depleted embryos exhibit colonic aganglionosis, a disorder in which the hindgut is devoid of neurons. Accordingly, the expression of Shh pathway components, previously shown to have a role in the etiology of Hirschsprung's disease, was misregulated within the gut following loss of Meis3. Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into and colonization of the gut such that its loss leads to severe defects in enteric nervous system development.

Additional Information

© 2015 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0). Submitted February 25, 2015. Revised August 6, 2015. Accepted September 2, 2015. Published online before print September 9, 2015. We would like to thank Charles Sagerström for the pCS2‐pbcab‐myc construct, Tatiana Hochgreb‐Hägele for foxa1 cDNA, Shuo Lin for pdx1 cDNA and Jeff Gross for ptch2 cDNA. We thank the Caltech Beckman Institute Biological Imaging Center and Fish Facility, Marcos Simões‐Costa for advice with double fluorescent in situ hybridization and Martha Henderson and David Mayorga for fish care. Research was supported from grants from NIH (DE024157) to M.E.B., from NIH F32 (HD080343) to R.A.U. and a Burroughs Wellcome Fund Postdoctoral Enrichment Program Fellowship to R.A.U.

Attached Files

Published - 3728.full.pdf

Supplemental Material - CombinedSupMats.pdf

Supplemental Material - mc-E15-02-0112-s01.mov

Supplemental Material - mc-E15-02-0112-s02.mov

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Created:
August 20, 2023
Modified:
October 24, 2023