Fig. 8

Summary of the effects on RHOA activity and NC polarity following manipulation of DLC1 and NEDD9 functions. a SOX9 induces SOX10 to activate DLC1 expression (dotted arrows indicate transactivation is likely to be indirect), while SOX9 directly transactivates NEDD9 expression through binding to its enhancer regions. NEDD9 is required for the polarized expression of DLC1 and their interaction is crucial for the establishment of high RHOA activity at the back and low at the front that directs polarized NC morphology and motility. b Overexpression of DN-DLC1 disrupts the interaction between endogenous DLC1-NEDD9 and other cofactors through sequestration, resulting in elevation of RHOA activity throughout the cell and unpolarized NC morphology with defective motility. c Excessive amount of DLC1 inhibits RHOA activity throughout the cell, resulting in lack of polarized NC morphology and loss of directionality. d Expression of NEDD9-MO leads to lack of polarized DLC1 expression that in turn disrupts asymmetric distribution of active RHOA between the back and front of NCC which exhibits unpolarized morphology and limited motility