Mechanisms Regulating Epithelial Integrity Directly Affect Facial Development

Published February 2022 | Current Topics in Developmental Biology

Two experts at Cincinnati Children’s are helping write the book for future scientists to understand the latest discoveries about molecular mechanisms that lead to conditions such as cleft palate.

Craniofacial malformations, including cleft lip and cleft palate, are among the most common structural birth defects, but the etiology and pathogenic mechanisms underlying these birth defects are not well understood.

This book chapter co-authored by Yu Lan, PhD, and Rulang Jiang, PhD, summarizes a collection of mouse genetic studies that have been instrumental in unraveling the mechanisms regulating epithelial integrity and periderm differentiation during facial and palate development. The chapter describes the beginnings of embryonic facial development as cranial neural crest cells interact with the surface ectoderm to form the facial primordia, and the crucial differentiation steps that occur as the facial primordial tissues grow and merge around the oral cavity to form the face and palate.

Disrupting periderm differentiation causes aberrant inter-epithelial adhesions that can interfere with facial morphogenesis. While formation of the upper lip requires adhesion followed by dissolution of intervening epithelial seams, palate formation involves adhesion and fusion of bilateral palatal shelves. The co-authors summarize findings of many gene mutations affecting cell adhesion molecules or their regulation in patients with cleft lip/palate and describe how mouse genetic studies have revealed underlying molecular mechanisms involving these factors.

“Since proper epithelial integrity also plays crucial roles in wound healing and cancer, understanding the mechanisms regulating epithelial integrity during facial development has direct implications for improvement in clinical care of craniofacial patients,” the co-authors state.

The chapter appears as part of a text entitled Mouse Models of Development and Disease, edited by Thomas Gridley and Leif Oxburgh.