Fig. 9.

A working model of the roles of Rho GTPases in endodermal polarity and organ bud development. (A) In the ventral endoderm CDC42 is required for apical PARD6B, which interacts with CDC42 to control cell shape, polarity (including apical F-actin accumulation), junction formation and cell viability. Within the thyroid bud, CDC42 is necessary for the apical accumulation of SHROOM3 and activated (phosphorylated) non-muscle myosin II, which promote the cytoskeletal contraction necessary for apical constriction and downward growth of the bud. The dotted line indicates that it is not clear whether this is via a direct interaction or through effects on cell polarity. SHROOM3 is required for thyroid bud apical constriction, but CDC42 is also necessary for expansion of the bud. Lack of bud expansion in CDC42 deficient embryos may be due to the structural abnormality of the adjacent endoderm cells that impedes their recruitment to the thyroid bud. F-actin (red), adherens junctions (green) and tight junctions (yellow). (B) Cdc42 and Rhou (Loebel et al., 2011) are both required for proper endoderm morphogenesis and affect cell polarity and shape. This may be due to an interaction with PARD6B. CDC42 and RHOU both affect the actin cytoskeleton, but CDC42 plays an additional role in apical junction formation. (C) CDC42 plays a role in expansion of hepatoblasts in the liver bud and for growth of the lung bud. Later in development, CDC42 influences branching morphogenesis in the lung. In the thyroid, down-regulation of Rhou coincides with the onset of multi-layering (Loebel et al., 2011) and CDC42, acting via SHROOM3, affects polarized protein distribution and apical constriction. CDC42 is further required for growth of the bud.