Diagram showing the effect of Sip1 knockdown on neural crest EMT. Our results show that NC cells undergoing the process of EMT go through two separate steps to become fully mesenchymal: (1) detachment from the neural tube and (2) separation from the ectoderm and dissociation from the other migratory NC cells. Compared with ContMO or untreated NC cells (left side), loss of Sip1 (right side) has no effect on step 1, but blocks step 2 due to the increased cell–cell adhesion caused by increased Ecad in the neural tube, epidermis, and migratory NC cells (red) and the loss of Ncad expression in the neural tube and migratory NC cells (orange). These data support a critical role for Sip1 in regulation of multiple adhesion molecules during neural crest EMT.