Basal Constriction During Brain Morphogenesis

The vertebrate brain develops from a tube, which becomes bent at stereotypical positions, to pack the brain into the skull. This packing protects the brain as a compact and stable structure. The first major bend to form separates the midbrain and hindbrain forming the midbrain-hindbrain boundary constriction (MHBC). Morphogenesis of the MHBC requires basal constriction, a novel cellular mechanism we described. This is in contrast to apical constriction, which has been extensively studied. Basal constriction occurs stepwise, in a group of cells that first basally constrict, before apically expanding to form wedge-shaped cells. An intact basement membrane is required, as sleepy mutants, corresponding to a Laminin chain, fail to undergo basal constriction. We have recently shown that focal adhesion kinase (FAK) is essential for basal constriction. Additionally, intact microtubules are essential for this process. We are presently addressing the connection between FAK, microtubules and other signaling modulators in basal constriction.