Role of the Extreme Anterior Domain Organizer in Craniofacial Development

Abstract

Craniofacial development is an intricate process, involving cranial neural crest (NC) and anterior facial tissue. NC migration is regulated by multiple mechanisms and activity of one or more organizer regions. Work presented here explores the role of the EAD, an organizer of craniofacial development in Xenopus, and its reciprocal signaling with cranial NC. The EAD later contributes to the mouth, nostrils, and anterior pituitary. EAD function involves the Kinin-Kallikrein pathway that was shown for the first time to be necessary for mouth formation. Facial transplants demonstrate that EAD-localized Kinin-Kallikrein function is required for migration of first arch cranial NC into the face. After migration, cranial NC signals back to the EAD to regulate mouth opening via the Wnt/PCP pathway. This pathway is associated with a process consistent with convergent extension of the EAD, whereby a wide and short epithelial mass narrows and lengthens, and cells and nuclei undergo stereotypical changes. The resultant EAD is a bilayered epithelium that later splits to form the mouth opening. Identification of the EAD as a NC organizer, reciprocal interaction of EAD and NC, and convergent extension associated with mouth formation has not previously been described during craniofacial development. Face formation is widely conserved, so findings in frog are likely relevant to amniotes and will provide insight into causes of craniofacial deformities.