Regulation of retinoic acid signaling during lung morphogenesis

• DOI: 10.1242/dev.127.14.3057
• Publication Date: 2021-04-26T04:09:49Z
• Authors: Sarah Malpel; Cathy Mendelsohn; Wellington V. Car...
• Keywords: Mesenchyme

Little is known about how retinoic acid (RA) synthesis, utilization and metabolism are regulated in the embryonic lung these activities relate to pattern formation. Here we report that early bud formation subsequent branching morphogenesis characterized by distinct stages of RA signaling. At onset development signaling ubiquitously activated primary buds, as shown expression major RA-synthesizing enzyme, RALDH-2 activation a RARE-lacZ transgene. Nevertheless, further airway appears require downregulation pathways decreased increased degradation epithelium via P450RAI-mediated metabolism, inhibition mesenchyme COUPTF-II expression. These mechanisms controlling local may be critical for normal branching, since show manipulating levels vitro maintain initial stage, leads an immature phenotype failure form typical distal buds. We this likely results from interfering with establishment center, altering distribution Fgf10 Bmp4, genes essential Furthermore, upregulates P450RAI expression, suggesting presence feedback availability. Our study illustrates importance regional control availability correct regulators during development.