Dislocated Tongue Muscle Attachment and XXXX Formation.

@entity4239 @entity19 @entity5104 @entity245 @entity17736 @entity2419 @entity121
UNASSIGNED: In Pierre Robin sequence, a retracted tongue due to @entity4239 is thought to physically obstruct palatal shelf elevation and thereby cause @entity2419 . However, @entity4239 is not always associated with palatal clefting. Here, by using the @entity17736 -null @entity19 model presenting with @entity2419 and severe @entity4239 , we provide the first causative mechanism linking the two. In wild-type embryos, the genioglossus muscle, which mediates tongue protrusion, originates from the rostral process of Meckel's cartilage and later from the mandibular symphysis, with 2 tendons positive for Scleraxis messenger RNA. In E13.5 @entity17736 -null embryos, a rostral process failed to form, and a mandibular symphysis was absent at E17.5. Consequently, the genioglossus muscle fibers were diverted toward the lingual surface of Meckel's cartilage and mandibles, where they attached in an aponeurosis that ectopically expressed Scleraxis. The deflection of genioglossus fibers from the anterior-posterior toward the medial-lateral axis alters their direction of contraction and necessarily compromises tongue protrusion. Since this @entity121 precedes palatal shelf elevation, it is likely to contribute to clefting. In contrast, embryos with a cranial mesenchyme-specific deletion of @entity17736 ( @entity17736 : @entity5104 -Cre) exhibited some degree of @entity4239 but no @entity2419 . In these embryos, a rostral process was present, indicating that mesenchyme-derived @entity17736 is dispensable for its formation. Moreover, the genioglossus appeared normal in @entity17736 : @entity5104 -Cre embryos, further supporting a role of aberrant tongue muscle attachment in palatal clefting. We thus propose that in Pierre Robin sequence, palatal shelf elevation is not impaired simply by physical obstruction by the tongue but by a specific @entity245 that leads to functional changes in tongue movements.
