TWIST IS REQUIRED IN HEAD MESENCHYME FOR CRANIAL NEURAL-TUBE MORPHOGENESIS

To understand the role of twist during mammalian development, we gener ated twist-null mice. twist-null embryos died at embryonic day 11.5. T heir most prominent phenotype was a failure of the cranial neural fold s to fuse. Mutant embryos also had defects in head mesenchyme, somites , and limb buds. Chimera analysis suggested that head mesenchyme was r equired for cranial neural tube closure and that twist acted in a cell -autonomous manner in this tissue. In addition, in the head mesenchyme region of chimeras, twist-null cells were segregated from wild-type c ells, and in the forebrain they lacked mesenchymal characteristics. Th ese results suggest that twist regulates the cellular phenotype and be havior of head mesenchyme cells that are essential for the subsequent formation of the cranial neural tube.