Threshold-specific requirements for Bmp4 in mandibular development.
Mandibular development is regulated by an interplay between a specified branchial arch ectoderm and a plastic mesenchyme. Moreover, signaling from the pharyngeal endoderm has been shown to be important for mandibular morphogenesis. To gain insight into the mechanisms regulating mandibular pattern, it is important to investigate the function of the epithelial-derived signals. Bmp4 is expressed in both distal, mandibular arch ectoderm and pharyngeal endoderm. Here, we show that deletion of Bmp4 in the mandibular ectoderm and to a lesser extent in the pharyngeal endoderm, resulted in severe defects in mandibular development. Furthermore, our data uncovered different Bmp4 thresholds for expression of the Bmp-dependent Msx1 and Msx2 genes in mandibular mesenchyme. We also found that ectodermal Fgf8 expression was both activated and repressed by Bmp4 in a dosage-dependent fashion indicating a novel Bmp4 function in threshold-specific regulation of Fgf8 transcription. Lastly, we provide evidence that Prx homeobox genes repress expression of an Msx2 transgene, previously shown to be Bmp4-responsive, revealing a mechanism for differential regulation of Msx1 and Msx2 by Bmp signaling.
Liu
Wei
W
Alkek Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, 77030, USA.
Selever
Jennifer
J
Murali
Deepa
D
Sun
Xiaoxia
X
Brugger
Sean M
SM
Ma
Lijiang
L
Schwartz
Robert J
RJ
Maxson
Robert
R
Furuta
Yasuhide
Y
Martin
James F
JF
D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001934:Branchial Region / Q000254:growth & development / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D051957:MSX1 Transcription Factor; D008334:Mandible / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D015398:Signal Transduction; D014158:Transcription, Genetic
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C496457:Fgf8 protein, mouse; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; C484084:Msx1 protein, mouse; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors