Figure 11

The role of Rho/Rock signaling in the molecular network underlying neural crest (NC) delamination. Opposite the segmental plate mesoderm, high levels of noggin result in low bone morphogenetic protein (BMP) activity, no Wnt1 transcription, low cyclin D1 in dorsal neural tube (NT) and no NC cells emigrating from the caudal NT. N-cadherin at this stage is expressed in the dorsal NT where it contributes to maintaining low cyclin D1 and lack of NC emigration. Rho activity through Rock helps maintaining membrane-bound N-cadherin and keeps a stable F-actin cytoskeleton. Together with the previous, direct N-cadherin-F-actin interactions contribute to the maintenance of epithelial premigratory NC. With ongoing development, opposite mature epithelial and dissociating somites, a factor emitted by the dorsomedial portion of the paraxial mesoderm inhibits noggin transcription in the NT, thereby relieving BMP activity. BMP4 in turn triggers Wnt1 transcription. Canonical Wnt signaling positively modulates transcription of cyclin D1, G1/S transition and NC cell delamination. In parallel, BMP4 via ADAM10 promotes N-cadherin cleavage into soluble CTF2. CTF2 may act in at least two ways, by upregulating β-catenin transcription and by binding β-catenin protein; we proposed that the complex translocates into the cell nucleus where transcription of target genes such as cyclin D1, followed by G1/S transition and epithelial-to-mesenchymal transition (EMT) of NC are stimulated. Hence, BMP activity transforms N-cadherin into a stimulatory signal (for details, see [31]. Concomitant with delamination, membrane-bound Rho proteins are downregulated, suggesting reduced activities of both Rho and Rock proteins; consequently, a dynamic turnover of stress fibers is made possible and N-cadherin association to the membrane is relieved. Altogether, these processes are compatible with generation of cellular movement downstream of the G1/S transition phase.