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Cranial neural crest cells (cNCCs) originate in the anterior neural tube and populate pharyngeal arches in which they contribute to formation of bone and cartilage. This cell population also provides molecular signals for the development of tissues of non-neural crest origin, such as the tongue muscles, teeth enamel or gland epithelium. Here we show that the transcription factor Meis2 is expressed in the oral region of the first pharyngeal arch (PA1) and later in the tongue primordium. Conditional inactivation of Meis2 in cNCCs resulted in loss of Sonic hedgehog signalling in the oropharyngeal epithelium and impaired patterning of PA1 along the lateral-medial and oral-aboral axis. Failure of molecular specification of PA1, illustrated by altered expression of Hand1/2 , Dlx5 , Barx1 , Gsc and other markers, led to hypoplastic tongue and ectopic ossification of the mandible. Meis2 -mutant mice thus display craniofacial defects that are reminiscent of several human syndromes and patients with mutations in the Meis2 gene.

Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway