Loss of p130Cas/Bcar1 impairs palatal mesenchymal expansion and causes cleft palate
5 affiliations
- 1Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University
- 2Department of Human, Information and Life Sciences, School of Health Sciences, University of Occupational and Environmental Health
- 3Department of Orthopedic Surgery, National Rehabilitation Center for Persons with Disabilities
- 4Field of Human Disease Models, Major in Advanced Life Sciences and Medicine, Institute of Laboratory Animals, Tokyo Women’s Medical University
- 5Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University
Abstract
Palatogenesis is a complex developmental process that requires the coordinated growth, elevation, and fusion of palatal shelves. Disruption of these events results in cleft palate, which is one of the most common congenital, craniofacial anomalies. p130Crk-associated substrate (p130Cas), also known as breast cancer anti-estrogen resistance 1 (BCAR1), is an adaptor protein involved in integrin-mediated signaling and cytoskeletal regulation; however, its role in late embryonic development is poorly understood because global p130Cas-deficiency leads to early embryonic lethality. In the present study, tamoxifen-inducible conditional knockout mice were used to investigate the role of p130Cas in palatal development. Conditional deletion of p130Cas resulted in cleft palate, characterized by impaired horizontal growth of the palatal shelves. Reduced mesenchymal cell proliferation within the palatal shelves was confirmed using Ki-67 immunostaining and EdU incorporation assays. Primary mouse embryonic palatal mesenchymal (MEPM) cells derived from p130Cas-deficient embryos consistently exhibited impaired proliferation and migration in vitro. The epithelial-specific deletion of p130Cas did not result in cleft palate, indicating that p130Cas function in the palatal mesenchyme is critical for normal palatal development. Taken together, these findings indicate that p130Cas is an important regulator of palatal mesenchymal expansion during secondary palatogenesis. The impaired proliferative growth of the palatal mesenchyme likely underlies the developmental basis of cleft palate in this model.
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BibTeX
@article{han2026loss,
title = {{Loss of p130Cas/Bcar1 impairs palatal mesenchymal expansion and causes cleft palate}},
author = {Tao Han and Jing Gao and Wei Wu and Mitsushiro Nakatomi and Ichiro Nakamura and Hiroaki Honda and Sho Tsukamoto and Takenobu Katagiri and Eijiro Jimi},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-62028-x},
url = {https://doi.org/10.1038/s41598-026-62028-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Loss of p130Cas/Bcar1 impairs palatal mesenchymal expansion and causes cleft palate
AU - Tao Han
AU - Jing Gao
AU - Wei Wu
AU - Mitsushiro Nakatomi
AU - Ichiro Nakamura
AU - Hiroaki Honda
AU - Sho Tsukamoto
AU - Takenobu Katagiri
AU - Eijiro Jimi
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-62028-x
UR - https://doi.org/10.1038/s41598-026-62028-x
AB - Palatogenesis is a complex developmental process that requires the coordinated growth, elevation, and fusion of palatal shelves. Disruption of these events results in cleft palate, which is one of the most common congenital, craniofacial anomalies. p130Crk-associated substrate (p130Cas), also known as breast cancer anti-estrogen resistance 1 (BCAR1), is an adaptor protein involved in integrin-mediated signaling and cytoskeletal regulation; however, its role in late embryonic development is poorly understood because global p130Cas-deficiency leads to early embryonic lethality. In the present study, tamoxifen-inducible conditional knockout mice were used to investigate the role of p130Cas in palatal development. Conditional deletion of p130Cas resulted in cleft palate, characterized by impaired horizontal growth of the palatal shelves. Reduced mesenchymal cell proliferation within the palatal shelves was confirmed using Ki-67 immunostaining and EdU incorporation assays. Primary mouse embryonic palatal mesenchymal (MEPM) cells derived from p130Cas-deficient embryos consistently exhibited impaired proliferation and migration in vitro. The epithelial-specific deletion of p130Cas did not result in cleft palate, indicating that p130Cas function in the palatal mesenchyme is critical for normal palatal development. Taken together, these findings indicate that p130Cas is an important regulator of palatal mesenchymal expansion during secondary palatogenesis. The impaired proliferative growth of the palatal mesenchyme likely underlies the developmental basis of cleft palate in this model.
SN - 2045-2322
ER -