A regulatory network controls nephrocan expression and midgut patterning.
Development
; 141(19): 3772-81, 2014 Oct.
Article
in En
| MEDLINE
| ID: mdl-25209250
ABSTRACT
Although many regulatory networks involved in defining definitive endoderm have been identified, the mechanisms through which these networks interact to pattern the endoderm are less well understood. To explore the mechanisms involved in midgut patterning, we dissected the transcriptional regulatory elements of nephrocan (Nepn), the earliest known midgut specific gene in mice. We observed that Nepn expression is dramatically reduced in Sox17(-/-) and Raldh2(-/-) embryos compared with wild-type embryos. We further show that Nepn is directly regulated by Sox17 and the retinoic acid (RA) receptor via two enhancer elements located upstream of the gene. Moreover, Nepn expression is modulated by Activin signaling, with high levels inhibiting and low levels enhancing RA-dependent expression. In Foxh1(-/-) embryos in which Nodal signaling is reduced, the Nepn expression domain is expanded into the anterior gut region, confirming that Nodal signaling can modulate its expression in vivo. Together, Sox17 is required for Nepn expression in the definitive endoderm, while RA signaling restricts expression to the midgut region. A balance of Nodal/Activin signaling regulates the anterior boundary of the midgut expression domain.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glycoproteins
/
Signal Transduction
/
Gene Expression Regulation, Developmental
/
Body Patterning
/
Gastrointestinal Tract
/
Endoderm
/
Gene Regulatory Networks
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Development
Journal subject:
BIOLOGIA
/
EMBRIOLOGIA
Year:
2014
Document type:
Article
Affiliation country:
Canadá