MFCS4 in palate development

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MFCS4 is one of cis-regulatory sequence for Shh transcription and its activation was found in oral and pharyngeal region from E11.00-E15.50. Compound deletion heterozygotes for Shh and MFCS4 show cleft palate. In palatal development, elevation of palatal shelves is achieved by corporation of intrinsic elevation force and change in shape and motion of the tongue. Because the palate of the mutant without tongue in organ culture successfully elevated and the exterior and histological preparation of the mutant tongue was hypomorphic, we focused on the relationship between tongue development and Shh signaling. In the tongue of the mutant, arrangement of the myotube was not organized or symmetric. Basal membrane of lingual epithelium that was discontinuous and without wave, and lingual septum that was again discontinuous and hypomorphic, were suggested to cause myotube disarrangement. As Shh signaling was previously reported to regulate the expression of laminin, that is a key component for basal membrane, and Sox9, that is a master transcription factor for tendon development, histological significances found in the tongue of the mutant agree with molecular mechanisms. These findings will be published with molecular evidences.