Genetic dissection of ventral folding morphogenesis in mouse: embryonic visceral endoderm-supplied BMP2 positions head and heart.

Ventral folding morphogenesis (VFM), a vital morphogenetic process in amniotes, mediates gut endoderm internalization, linear heart tube formation, ventral body wall closure and encasement of the fetus in extraembryonic membranes. Aberrant VFM underlies a number of birth defects such as gastroschisis and ectopia cordis in human and misplacement of head and heart in mouse. Recent cell lineage-specific mouse mutant analyses identified the Bone Morphogenetic Protein (BMP) pathway and Anterior Visceral Endoderm (AVE) as key regulators of anterior VFM. Loss of BMP2 expression solely from embryonic visceral endoderm (EmVE) and the AVE blocks formation of foregut invagination, and simultaneously, aberrantly positions the heart anterior/dorsal to the head, suggesting a mechanistic link between foregut and head/heart morphogenesis.