Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling
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 tongue swelling formation. 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 to disturb cellular processes which were disrupted in mutant mice. Our results provide hints for possible future treatment in ciliopathies.
Authors
- Satoshi Maruyama (ORCID: https://orcid.org/0000-0001-9036-1536)
- Yuan Kogure
- Yoshito Kakihara (ORCID: https://orcid.org/0000-0002-6014-8707)
- Paul T. Sharpe (ORCID: https://orcid.org/0000-0003-2116-9561)
- Atsushi Ohazama (ORCID: https://orcid.org/0000-0002-3496-0347)
- Madoka Kitamura
- Brunella Franco (ORCID: https://orcid.org/0000-0001-5588-4569)
- Fumiya Meguro
- Takahiro Nagai (ORCID: https://orcid.org/0000-0002-2538-486X)
- Jun Nihara (ORCID: https://orcid.org/0000-0002-4811-3077)
- Takayuki Nishimura (ORCID: https://orcid.org/0000-0001-5791-7512)
- Sarah Ghafoor (ORCID: https://orcid.org/0000-0002-3521-5955)
- Jun‐ichi Tanuma (ORCID: https://orcid.org/0000-0002-3896-9517)
- Takehisa Kudo
- Finsa Tisna Sari
- Martyn T. Cobourne (ORCID: https://orcid.org/0000-0003-2857-0315)
- Pierre Corre (ORCID: https://orcid.org/0000-0003-4587-2163)
- Roman Hossein Khonsari (ORCID: https://orcid.org/0000-0002-0649-1432)
- Takeyasu Maeda (ORCID: https://orcid.org/0000-0001-5317-7510)
- Yoko Ishida (ORCID: https://orcid.org/0009-0004-2710-3875)
- Alex Kesuma (ORCID: https://orcid.org/0009-0004-4076-7481)
- Vanessa Utama (ORCID: https://orcid.org/0000-0003-0630-610X)
- Maiko Kawasaki
- Katsushige Kawasaki (ORCID: https://orcid.org/0009-0000-1816-1337)
- Akira Fujita
Institutions
- Guy's Hospital (GB)
- King's College London (GB)
- Istituto Universitario di Studi Superiori di Pavia (IT)
- Centre Hospitalier Universitaire de Nantes (FR)
- Federico II University Hospital (IT)
- Scuola Superiore Meridionale (IT)
- Telethon Institute Of Genetics And Medicine (IT)
- Niigata University (JP)
Publication Details
- Journal
- eLife
- Published
- 2024-09-05
- DOI
- https://doi.org/10.7554/elife.85042
- Citations
- 3
- Primary Topic
- Genetic and Kidney Cyst Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.65
Funders
- Japan Society for the Promotion of Science