Cleft lip is one of the most common birth defects in humans, affecting 1/500-1/1000 live births, and results from incomplete fusion of the frontonasal and maxillary prominences during craniofacial morphogenesis. Despite its prevalence, the cellular and molecular mechanisms underlying fusion remain incompletely understood. In mouse, apoptosis of epithelial cells at the lambdoidal junction (λ) where the prominences meet has been shown to be essential for fusion, but other cellular behaviours – such as epithelial-mesenchymal transition (EMT) – have also been suggested to play a role. Now, Licia Selleri and colleagues further investigate the mechanisms underlying fusion of the facial prominences. They have previously shown that the Pbx transcription factors are required for epithelial cell apoptosis. Now, they demonstrate that not only is apoptosis insufficient to account for fusion, but also that Pbx promotes EMT at the λ. Pbx acts at least in part by directly promoting the expression of Snail1, a well-known activator of EMT. Their results support a model whereby apoptosis and EMT are sequential Pbx-dependent cellular behaviours deployed in the embryo to remove epithelial cells at the λ and thus achieve fusion. Since PBX1 expression was recently identified as a predictor of poor survival in patients with metastatic tumours, this study brings new insight into how Pbx-driven EMT executes morphogenesis as well as cancer invasion.
Probing the causes of cleft lip
Probing the causes of cleft lip. Development 1 March 2018; 145 (5): e0501. doi:
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