BMP receptor 1b is required for axon guidance and cell survival in the developing retina.
Previous work has documented the importance of BMPs in eye development. Loss-of-function studies in mice, with targeted deletions in either the Bmp7 or Bmp4 genes, have shown that these molecules are critical for early eye development. On the basis of the asymmetry in the dorsal-ventral expression patterns of several members of this family, it has been proposed that these molecules are critical for some aspect of dorsal-ventral patterning in the eye; however, it has been difficult to test this hypothesis because of the early requirement for BMPs in eye development. We have therefore examined the effects of loss of one of the BMP receptors, the BmprIb, on the development of the eye by using targeted deletion. We have found that BmprIb is expressed exclusively in the ventral retina during embryonic development and is required for normal ventral ganglion cell axon targeting to the optic nerve head. In mice with a targeted deletion of the BmprIb gene, many axons arising from the ventrally located ganglion cells fail to enter the optic nerve head, and instead, make abrupt turns in this region. A second phenotype in these mice is a significantly elevated inner retinal apoptosis during a distinct phase of postnatal development, at the end of neurogenesis. Our results therefore show two distinct requirements for BmprIb in mammalian retinal development.
Liu
Janice
J
Department of Biological Structure, University of Washington, School of Medicine, Seattle, WA 98195, USA. tomreh@u.washington.edu
Wilson
Steven
S
Reh
Thomas
T
D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000648:ultrastructure; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D002470:Cell Survival; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009900:Optic Nerve / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D017978:Receptors, Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D012165:Retinal Ganglion Cells / Q000502:physiology
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D017346:Protein Serine-Threonine Kinases; C498215:Bmpr1b protein, mouse; D052004:Bone Morphogenetic Protein Receptors; D052005:Bone Morphogenetic Protein Receptors, Type I