
Proper coordination of cell-cell interactions, migration, and differentiation processes in cranial neural crest cells and mesoderm-derived cells is essential for normal tongue development. Genetic or mechanical disruption of these coordinated cellular processes can lead to a range of congenital tongue anomalies.


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Dysfunction of primary cilia leads to genetic disorder, ciliopathies, which shows various malformations in many vital organs such as brain. Multiple tongue deformities including cleft, hamartoma and ankyloglossia are also seen in ciliopathies, which yield difficulties in fundamental functions such as mastication and vocalization. Here, we found these tongue anomalies in mice with mutation of ciliary protein. Abnormal cranial neural crest-derived cells (CNCC) failed to evoke Hh signal for differentiation of mesoderm-derived cells into myoblasts, which resulted in abnormal differentiation of mesoderm-derived cells into adipocytes. The ectopic adipose subsequently arrested migration of other mesoderm-derived cells and CNCC. Some aberrant CNCC abnormally differentiated into osteoblasts due to the lack of Hh signal, which migrated into tongue to form ectopic bone. Ankyloglossia was caused by aberrant cell migration due to lack of non-canonical Wnt signaling. In addition to ciliopathies, these tongue anomalies are often observed as non-familial condition in human. We found that these tongue deformities could be reproduced in wild-type mice by simple mechanical manipulations in CNCC to disturb cellular processes which were disrupted in mutant mice. Thus, tongue development requires coordinated multiple cellular processes (cell-cell contact, migration and differentiation). Our results provide hints for possible future treatment in ciliopathies.

### Competing Interest Statement

The authors have declared no competing interest.

Coordinated multiple cellular processes in tongue development

genetic-and-mechanical-disruption-of-coordinated-cellular-processes-leads-to-congenital-tongue-malformations


Genetic and Mechanical Disruption of Coordinated Cellular Processes Leads to Congenital Tongue Malformations
