Interplay of canonical and LIMK mediated non-canonical BMP signaling is essential for regulating differential thickness and invagination during chick forebrain roof plate morphogenesis

Telencephalic hemisphere formation is a complex and precisely timed process, which begins in the chick forebrain with an invagination in the middle of the roof plate. However, the factor(s) that determine the position/site of invagination in the roof plate remain to be elucidated. In this study, we have demonstrated that as development proceeds, a region of lower thickness appears in the middle of the roof plate, which marks the position where the invagination begins. Our investigations have implicated an interplay between the canonical (pSMAD 1/5/9 dependent) and the non-canonical (LIMK dependent) arms of BMP signaling in regulating this process. We have demonstrated that LIMK dependent non-canonical BMP signaling induces high levels of phosphorylated Cofilin (pCofilin) in the middle of the roof plate, which in turn alters Actin cytoskeleton dynamics, resulting in this region being thinner than the lateral regions. This study has provided the first mechanistic insight into how forebrain roof plate invagination begins and has thrown light on the role played by BMP signaling in this process.