New insights into craniofacial morphogenesis

Abstract

No region of our anatomy more powerfully conveys our emotions nor elicits more profound reactions when disease or genetic disorders disfigure it than the face. Recent progress has been made towards defining the tissue interactions and molecular mechanisms that control craniofacial morphogenesis. Some insights have come from genetic manipulations and others from tissue recombinations and biochemical approaches, which have revealed the molecular underpinnings of facial morphogenesis. Changes in craniofacial architecture also lie at the heart of evolutionary adaptation, as new studies in fish and fowl attest. Together, these findings reveal much about molecular and tissue interactions behind craniofacial development.

Development of the upper lip: Morphogenetic and molecular mechanisms

“…Because most of the craniofacial mesenchyme is derived from neural crest cells, genes and molecular pathways regulating neural crest formation, migration, patterning, proliferation, and apoptosis, are all important for craniofacial development. Various aspects of cranial neural crest development and the roles of neural crest in craniofacial development have been reviewed recently by others (e.g., Wilkie and Morris-Kay, 2001;Chambers and McGonnell, 2002;Basch et al, 2004;Cox, 2004;Huang and Saint-Jeannet, 2004;Graham et al, 2004;Kulesa et al, 2004;Marazita and Mooney, 2004;Helms et al, 2005). We will focus on discussing the genes and molecular pathways critical for upper lip morphogenesis after the five facial prominences have formed.…”

“…Furthermore, genetic variation at some loci likely sensitizes the embryo to other genetic and environmental insults. For example, modifications of Bmp4 expression or activity have been implicated in the evolution of facial shape in fish and birds (reviewed in Helms et al, 2005). Bmp4 is an essential regulator of facial primordial outgrowth and lip fusion, as discussed above.…”

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins

“…The mature mammalian face is formed by the fusion of seven facial primordia (Helms et al, 2005): the frontal nasal process (FNP), paired lateral nasal processes (LNPs), paired maxillary processes (MxPs), and paired mandibular processes (MnPs). The cellular and molecular events underlying craniofacial formation are complex, but there is a growing appreciation that the growth and patterning of the facial primordia has many parallels with development of the limb buds (Mariani and Martin, 2003;Niswander, 2003;Tickle, 2003;Helms et al, 2005).…”

“…The cellular and molecular events underlying craniofacial formation are complex, but there is a growing appreciation that the growth and patterning of the facial primordia has many parallels with development of the limb buds (Mariani and Martin, 2003;Niswander, 2003;Tickle, 2003;Helms et al, 2005). The genetic defects responsible for several human craniofacial syndromes are often accompanied by limb defects (Wilkie and MorrissKay, 2001;Ornitz and Marie, 2002;Thyagarajan et al, 2003;Zelzer and Olsen, 2003;Chen and Deng, 2005;L'Hote and Knowles, 2005), and mutations in a number of mouse genes can also cause morphological alterations in both the face and the limbs (Richman and Lee, 2003;Helms et al, 2005). In molecular terms, the two developmental systems rely on a combination of sonic hedgehog (shh) and fibroblast growth factor (FGF) signals to impart both survival and polarity information (Hu et al, 2003;Mariani and Martin, 2003;Niswander, 2003;Richman and Lee, 2003;Tickle, 2003;Abzhanov and Tabin, 2004;Helms et al, 2005).…”

“…The genetic defects responsible for several human craniofacial syndromes are often accompanied by limb defects (Wilkie and MorrissKay, 2001;Ornitz and Marie, 2002;Thyagarajan et al, 2003;Zelzer and Olsen, 2003;Chen and Deng, 2005;L'Hote and Knowles, 2005), and mutations in a number of mouse genes can also cause morphological alterations in both the face and the limbs (Richman and Lee, 2003;Helms et al, 2005). In molecular terms, the two developmental systems rely on a combination of sonic hedgehog (shh) and fibroblast growth factor (FGF) signals to impart both survival and polarity information (Hu et al, 2003;Mariani and Martin, 2003;Niswander, 2003;Richman and Lee, 2003;Tickle, 2003;Abzhanov and Tabin, 2004;Helms et al, 2005). Similarly, many transcription factors are utilized during both face and limb development, and mouse models with disrupted expression of these transcription factors often result in both craniofacial and limb defects.…”