B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/smad signaling.
Btg2 is a primary p53 transcriptional target gene which may function as a coactivator-corepressor and/or an adaptor molecule that modulates the activities of its interacting proteins. We have generated Btg2-null mice to elucidate the in vivo function of Btg2. Btg2-null mice are viable and fertile but exhibit posterior homeotic transformations of the axial vertebrae in a dose-dependent manner. Consistent with its role in vertebral patterning, Btg2 is expressed in the presomitic mesoderm, tail bud, and somites during somitogenesis. We further provide biochemical evidence that Btg2 interacts with bone morphogenetic protein (BMP)-activated Smads and enhances the transcriptional activity of BMP signaling. In view of the genetic evidence that reduced BMP signaling causes posteriorization of the vertebral pattern, we propose that the observed vertebral phenotype in Btg2-null mice is due to attenuated BMP signaling.
Park
Sean
S
Department of Physiology and Functional Genomics, University of Florida, 1600 SW Archer Rd., Room D533d, Gainesville, FL 32610, USA.
Lee
Young Jae
YJ
Lee
Ho-Jae
HJ
Seki
Tsugio
T
Hong
Kwon-Ho
KH
Park
Joonil
J
Beppu
Hideyuki
H
Lim
In Kyung
IK
Yoon
Ji-Won
JW
Li
En
E
Kim
Seong-Jin
SJ
Oh
S Paul
SP
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D019521:Body Patterning; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins; D013234:Stem Cells / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
C489435:Btg2 protein, mouse; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins