Selective Regulation of Arterial Branching Morphogenesis by Synectin

Abstract

Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched, stunted, and thin intersomitic vessels due to impaired migration and proliferation of angioblasts and arterial endothelial cells while not affecting venous development. Synectin(-/-) mice demonstrated decreased body and organ size, reduced numbers of arteries, and an altered pattern of arterial branching in multiple vascular beds while the venous system remained normal. Murine synectin(-/-) primary arterial, but not venous, endothelial cells showed decreased in vitro tube formation, migration, and proliferation and impaired polarization due to abnormal localization of activated Rac1. We conclude that synectin is involved in selective regulation of arterial, but not venous, growth and branching morphogenesis and that Rac1 plays an important role in this process.

Genotype–phenotype relationship in three cases with overlapping 19p13.12 microdeletions

“…Furthermore, no hearing loss was described in the Gipc1 knockout mouse. 16,17 Thus, the role of GIPC1 with respect to hearing impairment still remains to be clarified.…”

Rab13-dependent Trafficking of RhoA Is Required for Directional Migration and Angiogenesis

“…Cell Isolation and Culture-ECs from syx ϩ/ϩ and syx Ϫ/Ϫ hearts of adult mice of congenic C57/BL6 background were isolated as described (23) and maintained up to passage 5 in DMEM (Lonza Biowhittaker), 20% FBS (Fisher), 1% glutamate (Invitrogen), 1% nonessential amino acids (Invitrogen), 20 g/ml gentamycin (Sigma), and 100 g/ml EC mitogen supplement (Biomedical Technologies). The polyoma middle T-immortalized amot ϩ/ϩ and amot Ϫ/Ϫ ECs and their growth conditions were described previously (21).…”

GIPC1 Interacts with MyoGEF and Promotes MDA-MB-231 Breast Cancer Cell Invasion

“…Yeast two-hybrid screening led us to identify GIPC1 as an interacting partner of MyoGEF. GIPC1 plays a role in regulating cell migration (17)(18)(19)(20). Furthermore, GIPC1 levels increase in breast cancerous cells and tissues (24).…”

“…Accumulating evidence further indicates that GIPC1 plays a role in regulating cell polarity and motility. Murine primary arterial endothelial cells derived from GIPC1-ablated mice show decreased migration and impaired polarization (17). Syndecan-4, Syx1, and endoglin regulate cell migration through interactions with GIPC1/synectin (18 -20).…”