Article (Scientific journals)
The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine.
Flasse, Lydie; Stern, David; Pirson, Justine et al.
2013In Developmental Biology, 376 (2), p. 187-97
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Keywords :
Animals; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism/physiology; Cell Differentiation/genetics/physiology; Cell Lineage; Cell Proliferation; Enteroendocrine Cells/cytology; Gene Expression Regulation, Developmental; Intestines/embryology; Models, Biological; Mutation; Receptors, Notch/metabolism; Signal Transduction/genetics/physiology; Transcription Factors; Zebrafish; Zebrafish Proteins/genetics/physiology
Abstract :
[en] Notch signaling has a fundamental role in stem cell maintenance and in cell fate choice in the intestine of different species. Canonically, Notch signaling represses the expression of transcription factors of the achaete-scute like (ASCL) or atonal related protein (ARP) families. Identifying the ARP/ASCL genes expressed in the gastrointestinal tract is essential to build the regulatory cascade controlling the differentiation of gastrointestinal progenitors into the different intestinal cell types. The expression of the ARP/ASCL factors was analyzed in zebrafish to identify, among all the ARP/ASCL factors found in the zebrafish genome, those expressed in the gastrointestinal tract. ascl1a was found to be the earliest factor detected in the intestine. Loss-of-function analyses using the pia/ascl1a mutant, revealed that ascl1a is crucial for the differentiation of all secretory cells. Furthermore, we identify a battery of transcription factors expressed during secretory cell differentiation and downstream of ascl1a. Finally, we show that the repression of secretory cell fate by Notch signaling is mediated by the inhibition of ascl1a expression. In conclusion, this work identifies Ascl1a as a key regulator of the secretory cell lineage in the zebrafish intestine, playing the same role as Atoh1 in the mouse intestine. This highlights the diversity in the ARP/ASCL family members acting as cell fate determinants downstream from Notch signaling.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Flasse, Lydie 
Stern, David ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Pirson, Justine ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Manfroid, Isabelle ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Peers, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Voz, Marianne  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Language :
English
Title :
The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine.
Publication date :
2013
Journal title :
Developmental Biology
ISSN :
0012-1606
eISSN :
1095-564X
Publisher :
Elsevier, Atlanta, United States - Florida
Volume :
376
Issue :
2
Pages :
187-97
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2013 Elsevier Inc. All rights reserved.
Available on ORBi :
since 08 July 2013

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