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BMP signaling participates in late phase differentiation of the retina, partly via upregulation of Hey2
Author(s) -
Kuribayashi Hiroshi,
Baba Yukihiro,
Watanabe Sumiko
Publication year - 2014
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22196
Subject(s) - biology , microbiology and biotechnology , retinal , muller glia , retina , bone morphogenetic protein , signal transduction , bmpr2 , cellular differentiation , bone morphogenetic protein receptor , retinal regeneration , progenitor cell , stem cell , neuroscience , genetics , biochemistry , gene
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. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1172–1183, 2014