| First Author | Gao T | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 10 | PubMed ID | 33848271 |
| Mgi Jnum | J:308271 | Mgi Id | MGI:6727622 |
| Doi | 10.1172/jci.insight.145854 | Citation | Gao T, et al. (2021) Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system. JCI Insight 6(10) |
| abstractText | Retinoic acid (RA) signaling is essential for enteric nervous system (ENS) development, since vitamin A deficiency or mutations in RA signaling profoundly reduce bowel colonization by ENS precursors. These RA effects could occur because of RA activity within the ENS lineage or via RA activity in other cell types. To define cell-autonomous roles for retinoid signaling within the ENS lineage at distinct developmental time points, we activated a potent floxed dominant-negative RA receptor alpha (RaralphaDN) in the ENS using diverse CRE recombinase-expressing mouse lines. This strategy enabled us to block RA signaling at premigratory, migratory, and postmigratory stages for ENS precursors. We found that cell-autonomous loss of RA receptor (RAR) signaling dramatically affected ENS development. CRE activation of RaralphaDN expression at premigratory or migratory stages caused severe intestinal aganglionosis, but at later stages, RaralphaDN induced a broad range of phenotypes including hypoganglionosis, submucosal plexus loss, and abnormal neural differentiation. RNA sequencing highlighted distinct RA-regulated gene sets at different developmental stages. These studies show complicated context-dependent RA-mediated regulation of ENS development. |
