BCL11B regulates epithelial proliferation and asymmetric development of the mouse mandibular incisor.
Mouse incisors grow continuously throughout life with enamel deposition uniquely on the outer, or labial, side of the tooth. Asymmetric enamel deposition is due to the presence of enamel-secreting ameloblasts exclusively within the labial epithelium of the incisor. We have previously shown that mice lacking the transcription factor BCL11B/CTIP2 (BCL11B hereafter) exhibit severely disrupted ameloblast formation in the developing incisor. We now report that BCL11B is a key factor controlling epithelial proliferation and overall developmental asymmetry of the mouse incisor: BCL11B is necessary for proliferation of the labial epithelium and development of the epithelial stem cell niche, which gives rise to ameloblasts; conversely, BCL11B suppresses epithelial proliferation, and development of stem cells and ameloblasts on the inner, or lingual, side of the incisor. This bidirectional action of BCL11B in the incisor epithelia appears responsible for the asymmetry of ameloblast localization in developing incisor. Underlying these spatio-specific functions of BCL11B in incisor development is the regulation of a large gene network comprised of genes encoding several members of the FGF and TGFβ superfamilies, Sprouty proteins, and Sonic hedgehog. Our data integrate BCL11B into these pathways during incisor development and reveal the molecular mechanisms that underlie phenotypes of both Bcl11b(-/-) and Sprouty mutant mice.
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, United States of America.
Kateryna
K
Kyrylkova
Sergiy
S
Kyryachenko
Brian
B
Biehs
Ophir
O
Klein
Chrissa
C
Kioussi
Mark
M
Leid
D000565:Ameloblasts / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007180:Incisor / Q000254:growth & development* / Q000378:metabolism; D008334:Mandible / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009805:Odontogenesis / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C511143:Bcl11b protein, mouse; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins