PUBLICATION

In Toto imaging of early enteric nervous system Development reveals that gut colonization is tied to proliferation downstream of ret

Authors
Baker, P.A., Ibarra-García-Padilla, R., Venkatesh, A., Singleton, E.W., Uribe, R.A.
ID
ZDB-PUB-221028-33
Date
2022
Source
Development (Cambridge, England)   149(21): (Journal)
Registered Authors
Baker, Phillip, Singleton, Eileen, Uribe, Rosa
Keywords
Differentiation, Enteric nervous system, Enteric neural crest, Proliferation, Ret, Zebrafish
MeSH Terms
  • Animals
  • Cell Division
  • Cell Movement/genetics
  • Cell Proliferation
  • Enteric Nervous System*
  • Hirschsprung Disease*/genetics
  • Hirschsprung Disease*/metabolism
  • Humans
  • Intestines
  • Neural Crest
  • Proto-Oncogene Proteins c-ret/genetics
  • Proto-Oncogene Proteins c-ret/metabolism
  • Zebrafish/genetics
PubMed
36300492 Full text @ Development
Abstract
The enteric nervous system (ENS) is a vast intrinsic network of neurons and glia within the gastrointestinal tract and is largely derived from enteric neural crest cells (ENCCs) that emigrate into the gut during vertebrate embryonic development. Study of ENCC migration dynamics and their genetic regulators provides great insights into fundamentals of collective cell migration and nervous system formation, and are a pertinent subject for study due to their relevance to the human congenital disease, Hirschsprung disease (HSCR). For the first time, we performed in toto gut imaging and single-cell generation tracing of ENCC migration in WT and a novel ret heterozygous background zebrafish (retwmr1/+) to gain insight into ENCC dynamics in vivo. We observed that retwmr1/+ zebrafish produced fewer ENCCs while localized along the gut, which failed to reach the hindgut, resulting in HSCR-like phenotypes. Specifically, we observed a proliferation dependent migration mechanism, where cell divisions were associated with inter-cell distances and migration speed. Lastly, we detected a premature neuronal differentiation gene expression signature in retwmr1/+ ENCCs, collectively suggesting that Ret signaling may function to regulate maintenance of a stem-state in ENCCs.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping