Document Detail


Loss of ascl1a prevents secretory cell differentiation within the zebrafish intestinal epithelium resulting in a loss of distal intestinal motility.
MedLine Citation:
PMID:  23353550     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The vertebrate intestinal epithelium is renewed continuously from stem cells at the base of the crypt in mammals or base of the fold in fish over the life of the organism. As stem cells divide, newly formed epithelial cells make an initial choice between a secretory or enterocyte fate. This choice has previously been demonstrated to involve Notch signaling as well as Atonal and Her transcription factors in both embryogenesis and adults. Here, we demonstrate that in contrast to the atoh1 in mammals, ascl1a is responsible for formation of secretory cells in zebrafish. ascl1a-/- embryos lack all intestinal epithelial secretory cells and instead differentiate into enterocytes. ascl1a-/- embryos also fail to induce intestinal epithelial expression of deltaD suggesting that ascl1a plays a role in initiation of Notch signaling. Inhibition of Notch signaling increases the number of ascl1a and deltaD expressing intestinal epithelial cells as well as the number of developing secretory cells during two specific time periods: between 30 and 34hpf and again between 64 and 74hpf. Loss of enteroendocrine products results in loss of anterograde motility in ascl1a-/- embryos. 5HT produced by enterochromaffin cells is critical in motility and secretion within the intestine. We find that addition of exogenous 5HT to ascl1a-/- embryos at near physiological levels (measured by differential pulse voltammetry) induce anterograde motility at similar levels to wild type velocity, distance, and frequency. Removal or doubling the concentration of 5HT in WT embryos does not significantly affect anterograde motility, suggesting that the loss of additional enteroendocrine products in ascl1a-/- embryos also contributes to intestinal motility. Thus, zebrafish intestinal epithelial cells appear to have a common secretory progenitor from which all subtypes form. Loss of enteroendocrine cells reveals the critical need for enteroendocrine products in maintenance of normal intestinal motility.
Authors:
Gillian Roach; Rachel Heath Wallace; Amy Cameron; Rifat Emrah Ozel; Cintia F Hongay; Reshica Baral; Silvana Andreescu; Kenneth N Wallace
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-23
Journal Detail:
Title:  Developmental biology     Volume:  376     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-05-13     Revised Date:  2014-04-16    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  171-86     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics*,  physiology*
Cell Differentiation
Cell Lineage
Enterochromaffin Cells / cytology
Enterocytes / metabolism
Epithelial Cells / cytology*
Gastrointestinal Motility
Gene Expression Regulation, Developmental
Goblet Cells / cytology
Intestines / embryology*
Models, Biological
Models, Genetic
Mutation
Signal Transduction
Zebrafish
Zebrafish Proteins / genetics*,  physiology*
Grant Support
ID/Acronym/Agency:
1R15DK089474-01/DK/NIDDK NIH HHS; R15 DK089474/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Zebrafish Proteins; 0/achaete-scute complex-like 1a protein, zebrafish
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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