Abstract

Cleft palate is a common congenital birth defect in humans. In mammals, the palatal tissue can be distinguished into anterior bony hard palate and posterior muscular soft palate that have specialized functions in occlusion, speech or swallowing. Regulation of palate development appears to be the result of distinct signaling and genetic networks in the anterior and posterior regions of the palate. Development and maintenance of expression of these region-specific genes is crucial for normal palate development. Numerous transcription factors and signaling pathways are now recognized as either anterior- (e.g., Msx1, Bmp4, Bmp2, Shh, Spry2, Fgf10, Fgf7, and Shox2) or posterior-specific (e.g., Meox2, Tbx22, and Barx1). Localized expression and function clearly highlight the importance of regional patterning and differentiation within the palate at the molecular level. Here, we review how these molecular pathways and networks regulate the anterior–posterior patterning and development of secondary palate. We hypothesize that the anterior palate acts as a signaling center in setting up development of the secondary palate.

Highlights

  • Cleft palate is one of the most common congenital birth defects in humans, occurring with a frequency of 1:700 to 1:1000 live births (Gorlin et al, 2001)

  • The development of the secondary palate is regulated by a number of complex networks of growth factors and transcription factors

  • We hypothesize that the anterior palate acts as a signaling center for secondary palate patterning and development

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Summary

Introduction

Cleft palate is one of the most common congenital birth defects in humans, occurring with a frequency of 1:700 to 1:1000 live births (Gorlin et al, 2001). Hoxa2 null mice exhibit an 81% penetrance of cleft palate (Gendron-Maguire et al, 1993; Rijli et al, 1993; Barrow and Capecchi, 1999), which appears to result from increased cell proliferation where expression levels of both Msx1 and its known down-stream target Bmp4 are up-regulated during the early stages of palate development (Smith et al, 2009).

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