Distinct developmental programs require different levels of Bmp signaling during mouse retinal development.
The Bmp family of secreted signaling molecules is implicated in multiple aspects of embryonic development. However, the cell-type-specific requirements for this signaling pathway are often obscure in the context of complex embryonic tissue interactions. To define the cell-autonomous requirements for Bmp signaling, we have used a Cre-loxP strategy to delete Bmp receptor function specifically within the developing mouse retina. Disruption of a Bmp type I receptor gene, Bmpr1a, leads to no detectable eye abnormality. Further reduction of Bmp receptor activity by removing one functional copy of another Bmp type I receptor gene, Bmpr1b, in the retina-specific Bmpr1a mutant background, results in abnormal retinal dorsoventral patterning. Double mutants completely lacking both of these genes exhibit severe eye defects characterized by reduced growth of embryonic retina and failure of retinal neurogenesis. These studies provide direct genetic evidence that Bmpr1a and Bmpr1b play redundant roles during retinal development, and that different threshold levels of Bmp signaling regulate distinct developmental programs such as patterning, growth and differentiation of the retina.
Murali
Deepa
D
Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Yoshikawa
Shunichi
S
Corrigan
Rebecca R
RR
Plas
Daniel J
DJ
Crair
Michael C
MC
Oliver
Guillermo
G
Lyons
Karen M
KM
Mishina
Yuji
Y
Furuta
Yasuhide
Y
D000818:Animals; D019521:Body Patterning; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002874:Chromosome Mapping; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D009900:Optic Nerve / Q000196:embryology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes
D019485:Bone Morphogenetic Proteins; D017978:Receptors, Growth Factor; C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C498212:Bmpr1a protein, mouse; C498215:Bmpr1b protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I