DISRUPTION OF THE MACMARCKS GENE PREVENTS CRANIAL NEURAL-TUBE CLOSUREAND RESULTS IN ANENCEPHALY

MacMARCKS is a member of the MARCKS family of protein kinase C (PKC) s ubstrates. Biochemical evidence demonstrates that these proteins integ rate calcium and PKC-dependent signals to regulate actin structure at the membrane, We report here that deletion of the MacMARCKS gene preve nts cranial neural tube closure in the developing brain, resulting in anencephaly. This suggests a central role for MacMARCKS and the PKC si gnal transduction pathway in the folding of the anterior neural plate during the early phases of brain formation, and supports the hypothesi s that actin-based motility directs cranial neural tube closure.