Novel insights into a retinoic-acid-induced cleft palate based on Rac1 regulation of the fibronectin arrangement.
Retinoic acid (RA)-induced cleft palate results from both extrinsic obstructions by the tongue and internal factors within the palatal shelves. Our previous study showed that the spatiotemporal expression of Rac1 regulates the fibronectin (FN) arrangement through cell density alterations that play an important role in palate development. In this study, we investigate the involvement of the Rac1 regulation of the FN arrangement in RA-induced cleft palate. Our results demonstrate that RA-induced intrinsic alterations in palatal shelves, including a delayed progress of cell condensation, delay palate development, even after the removal of the tongue. Further analysis shows that RA treatment diminishes the region-distinctive expression of Rac1 within the palatal shelves, which reversely alters the fibrillar arrangement of FN. Furthermore, RA treatment disrupts the formation of lamellipodia, which are indicative structures of cell migration that are regulated by Rac1. These results suggest that the Rac1 regulation of the FN arrangement is involved in RA-induced cleft palate through the regulation of cell migration, which delays the progress of cell condensation and subsequently influences the FN arrangement, inducing a delay in palate development. Our study provides new insights into the RA-induced impairment of palatal shelf elevation based on cell migration dynamics.
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
Qinghuang
Q
Tang
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
Liwen
L
Li
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
Min-Jung
MJ
Lee
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea.
Qing
Q
Ge
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea. min@yuhs.ac.
Jong-Min
JM
Lee
Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Korea. hsj8076@gmail.com.|Oral Biosciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, SAR, People's Republic of China. hsj8076@gmail.com.
Han-Sung
HS
Jung
D000818:Animals; D002452:Cell Count; D002972:Cleft Palate / Q000139:chemically induced* / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D008648:Mesoderm / Q000473:pathology; D008813:Mice, Inbred ICR; D010159:Palate / Q000378:metabolism / Q000473:pathology; D011554:Pseudopodia / Q000378:metabolism; D014059:Tongue; D014212:Tretinoin; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D005353:Fibronectins; D014212:Tretinoin; D020830:rac1 GTP-Binding Protein
Cleft palate; Fibronectin; Mouse; Palatal shelf elevation; Rac1; Retinoic acid