title: BMP signaling participates in late phase differentiation of the retina, partly via upregulation of Hey2.
abstract: Bone morphogenetic protein (BMP) plays pivotal roles in early retinal development. However, its roles in the late phase of retinal development remain unclear. We found that BMP receptors and ligands were expressed in the postnatal mouse retina. Furthermore, immunostaining revealed that phosphorylated Smads were enriched in various cells types in the inner nuclear layer postnatally. However, phosphorylated Smads were not detected in photoreceptors, suggesting that BMP may play roles in retinal cells in the inner nuclear layer. Forced expression of constitutively active BMP receptors during retinal development resulted in an increased number of bipolar cells and Müller glia and a decreased number of rod photoreceptors; however, proliferation was not perturbed. The expression of dominant negative BMP receptors resulted in a decreased number of Müller glia and bipolar cells. In addition, inhibiting BMP signaling in retinal monolayer cultures abrogated Müller glial process extension, suggesting that BMP signaling also plays a role in the maturation of Müller glia. The expression of the basic helix-loop-helix transcription factor Hey2 was induced by BMP signaling in retinas. The coexpression of sh-Hey2 with constitutively active BMP receptors suggested that the effects of BMP signaling on retinal differentiation could be attributed partly to the induction of Hey2 by BMP. We propose that BMP signaling plays pivotal roles in the differentiation of retinal progenitor cells into late differentiating retinal cell types and in the maturation of Müller glia; these effects were mediated, at least in part, by Hey2.
authors.affiliation: Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuribayashi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Sumiko
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012160:Retina / Q000254:growth & development* / Q000502:physiology*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D046509:Tissue Culture Techniques; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D051798:Inhibitor of Differentiation Protein 1; D051880:Receptors, Notch; D012097:Repressor Proteins; D051785:Smad Proteins; C485778:Hey2 protein, mouse; C497455:Idb1 protein, mouse
keywords: BMP; differentiation; mouse; retina