Lineage-specific intersection of endothelin and GDNF signaling in enteric nervous system development.
| Autor: | Poltavski DM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, United States., Cunha AT; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, United States., Tan J; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, United States., Sucov HM; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, United States., Makita T; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, United States. |
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| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2024 Dec 06; Vol. 13. Date of Electronic Publication: 2024 Dec 06. |
| DOI: | 10.7554/eLife.96424 |
| Abstrakt: | Two major ligand-receptor signaling axes - endothelin Edn3 and its receptor Ednrb, and glial-derived neurotrophic factor (GDNF) and its receptor Ret - are required for migration of enteric nervous system (ENS) progenitors to the hindgut. Mutations in either component cause colonic aganglionosis, also called Hirschsprung disease. Here, we have used Wnt1Cre and Pax2Cre in mice to show that these driver lines label distinct ENS lineages during progenitor migration and in their terminal hindgut fates. Both Cre lines result in Hirschsprung disease when combined with conditional Ednrb or conditional Ret alleles. In vitro explant assays and analysis of lineage-labeled mutant embryos show that GDNF but not Edn3 is a migration cue for cells of both lineages. Instead, Edn3-Ednrb function is required in both for GDNF responsiveness albeit in different ways: by expanding the Ret + population in the Pax2Cre lineage, and by supporting Ret function in Wnt1Cre-derived cells. Our results demonstrate that two distinct lineages of progenitors give rise to the ENS, and that these divergently utilize endothelin signaling to support migration to the hindgut. Competing Interests: DP, AC, JT, HS, TM No competing interests declared (© 2024, Poltavski, Cunha et al.) |
| Databáze: | MEDLINE |
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