Dr. Kerstin Ludwig
Institute of Human Genetics
kerstin.ludwig@uni-bonn.de View member: Dr. Kerstin Ludwig
Development (Cambridge, England)
Nonsyndromic clefts of the lip and palate are common birth defects resulting from gene-gene and gene-environment interactions. Mutations in human have been linked to orofacial clefting and we show here that deficiency causes a growth defect of the medial nasal process (Mnp) in mouse embryos. Although this defect alone does not disrupt lip formation, -deficient embryos develop a cleft lip when the mother is transiently exposed to reduced oxygen levels or to phenytoin, a drug known to cause embryonic hypoxia. In the absence of interacting environmental factors, the Mnp growth defect caused by deficiency is modified by a -dependent 'morphogenetic regulation', which modulates Mnp shape, rescues lip formation and involves a localized abrogation of Bmp4-mediated repression of Analyses of GWAS data revealed a genome-wide significant association of a Gene Ontology morphogenesis term (including assigned roles for , , , and ) specifically for nonsyndromic cleft lip with cleft palate. Our data indicate that mutations could increase the risk for cleft lip formation by interacting with an impaired morphogenetic regulation that adjusts Mnp shape, or through interactions that inhibit Mnp growth.
© 2020. Published by The Company of Biologists Ltd.
PMID: 32467233
Institute of Human Genetics
kerstin.ludwig@uni-bonn.de View member: Dr. Kerstin Ludwig