|  Help  |  About  |  Contact Us

Publication : Mesenchymal cells regulate enteric neural crest cell migration via RET-GFRA1b trans-signaling.

First Author  Morikawa M Year  2024
Journal  Biochem Biophys Res Commun Volume  710
Pages  149861 PubMed ID  38581949
Mgi Jnum  J:347711 Mgi Id  MGI:7625487
Doi  10.1016/j.bbrc.2024.149861 Citation  Morikawa M, et al. (2024) Mesenchymal cells regulate enteric neural crest cell migration via RET-GFRA1b trans-signaling. Biochem Biophys Res Commun 710:149861
abstractText  During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11-12 (E11-12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12-13.5 revealed high levels of GFRA1 expression on the anti-mesenteric side of the hindgut, correlating with enhanced ENCC migration. This indicates that GFRA1 in EMCs plays a role in ENCC migration during development. Examining GFRA1 isoforms, we found high levels of GFRA1b, which lacks amino acids 140-144, in EMCs. To assess the impact of GFRA1 isoforms on EMC-ENCC communication, we conducted neurosphere drop assays. This revealed that GFRA1b-expressing cells promoted GDNF-dependent extension and increased neurite density in ENCC neurospheres. Co-culture of ENCC mimetic cells expressing RET and GFRA1a with EMC mimetic cells expressing GFRA1a, GFRA1b, or vector alone showed that only GFRA1b-expressing co-cultured cells sustained RET phosphorylation in ENCC-mimetic cells for over 120 min upon GDNF stimulation. Our study provides evidence that GFRA1b-mediated cell-to-cell communication plays a critical role in ENCC motility in enteric nervous system development. These findings contribute to understanding the cellular interactions and signaling mechanisms that underlie enteric nervous system formation and highlight potential therapeutic targets for gastrointestinal motility disorders.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

8 Bio Entities

Trail: Publication

87 Expression

Trail: Publication