The GEX-2 and GEX-3 proteins are required for tissue morphogenesis and cell migrations in C. elegans

Abstract

During body morphogenesis precisely coordinated cell movements and cell shape changes organize the newly differentiated cells of an embryo into functional tissues. Here we describe two genes, gex-2 and gex-3, whose activities are necessary for initial steps of body morphogenesis in Caenorhabditis elegans. In the absence of gex-2 and gex-3 activities, cells differentiate properly but fail to become organized. The external hypodermal cells fail to spread over and enclose the embryo and instead cluster on the dorsal side. Postembryonically gex-3 activity is required for egg laying and for proper morphogenesis of the gonad. GEX-2 and GEX-3 proteins colocalize to cell boundaries and appear to directly interact. GEX-2 and GEX-3 are highly conserved, with vertebrate homologs implicated in binding the small GTPase Rac and a GEX-3 Drosophila homolog, HEM2/NAP1/KETTE, that interacts genetically with Rac pathway mutants. Our findings suggest that GEX-2 and GEX-3 may function at cell boundaries to regulate cell migrations and cell shape changes required for proper morphogenesis and development.

Control of developmental networks by Rac/Rho small GTPases: How cytoskeletal changes during embryogenesis are orchestrated

“…Actomyosin contractility is essential for the ingression of cells during gastrulation 32. Gastrulation in C. elegans is not as spectacular as in many other animal embryos, because cells move only over short distances, and the blastocoel space is small 33 as can be observed in Supplementary Movie S1. CED‐10/Rac was shown to play an essential role during early C. elegans embryogenesis because C. elegans null homozygous ced‐10 /Rac mutant embryos arrest, manifesting defects in cell migration and gastrulation.…”

“…CED‐10/Rac was shown to play an essential role during early C. elegans embryogenesis because C. elegans null homozygous ced‐10 /Rac mutant embryos arrest, manifesting defects in cell migration and gastrulation. Most of these null ced‐10 /Rac mutant embryos exhibit a terminal phenotype in which the gut is present on the exterior of the embryo termed the Gex phenotype “gut on the exterior”; where endoderm cell types that are normally internal are located on the exterior of the embryo 33.…”

“…Simultaneously, on the dorsal side of the embryo, epidermal cells undergo cell intercalation and the embryo elongates 33, 37, 38.…”

“…CED‐10/Rac activates the WAVE/SCAR complex, which serves as an actin‐nucleation promoting factor to activate the Arp2/3 complex for the polymerization of short, branched F‐actin (Fig. 2) 33, 40, 41. Loss of CED‐10/Rac, any WAVE/SCAR component, or the Arp2/3 complex, blocks cell migrations of the embryonic epidermis, whereas cell differentiation remains unaffected, in all these cases the ventral epidermal cells remain unattached on both sides of the embryo.…”

“…Loss of CED‐10/Rac, any WAVE/SCAR component, or the Arp2/3 complex, blocks cell migrations of the embryonic epidermis, whereas cell differentiation remains unaffected, in all these cases the ventral epidermal cells remain unattached on both sides of the embryo. As a result, internal cells are not fully covered by epidermis, and extrude out during elongation of the embryo, causing a Gex phenotype 33, 40. CED‐10/Rac and MIG‐2/RhoG are also known to redundantly control the basolateral protrusive activity involved in cell rearrangements of dorsal epidermal cell intercalation 42.…”