Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C-cadherin adhesion activity.
Little is known about how protocadherins function in cell adhesion and tissue development. Paraxial protocadherin (PAPC) controls cell sorting and morphogenetic movements in the Xenopus laevis embryo. We find that PAPC mediates these functions by down-regulating the adhesion activity of C-cadherin. Expression of exogenous C-cadherin reverses PAPC-induced cell sorting and gastrulation defects. Moreover, loss of endogenous PAPC results in elevated C-cadherin adhesion activity in the dorsal mesoderm and interferes with the normal blastopore closure, a defect that can be rescued by a dominant-negative C-cadherin mutant. Importantly, activin induces PAPC expression, and PAPC is required for activin-induced regulation of C-cadherin adhesion activity and explant morphogenesis. Signaling through Frizzled-7 is not required for PAPC regulation of C-cadherin, suggesting that C-cadherin regulation and Frizzled-7 signaling are two distinct branches of the PAPC pathway that induce morphogenetic movements. Thus, spatial regulation of classical cadherin adhesive function by local expression of a protocadherin is a novel mechanism for controlling cell sorting and tissue morphogenesis.
Chen
Xuejun
X
Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Gumbiner
Barry M
BM
D028341:Activins / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000196:embryology; D005775:Gastrula / Q000166:cytology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
C074260:CDH3 protein, Xenopus; D015820:Cadherins; C492040:Fzd7 protein, Xenopus; C117635:Pcdh8 protein, Xenopus; D000091363:Protocadherins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins; D028341:Activins