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Conference Paper: Activation of Id genes by BMP signaling influences proliferation and cell fate choices of retinal progenitors

TitleActivation of Id genes by BMP signaling influences proliferation and cell fate choices of retinal progenitors
Authors
Issue Date2010
PublisherAssociation for Research in Vision and Ophthalmology
Citation
Association for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, FL., 2-6 May 2010. In Investigative Ophthalmology & Visual Science, 2010, v. 51 n. 13, Abstract no. 2655 How to Cite?
AbstractIntroduction: : Purposes: Bone morphogenetic proteins (BMPs) are multi-functional growth factors, and are well-known for regulating eye development in diverse aspects. It is also known that BMP signaling is essential for embryonic development and cellular functions such as cell growth, fate determination, differentiation and apoptosis. Inhibitors of differentiation (Id) proteins have emerged recently as the critical targets of BMPs. Id proteins are known to be important mediators of BMPs and the regulation of Id protein by BMPs is mainly through a Smad-dependent pathway. Our previous work showed that BMPs and BMPRs were co-expressed with Ids mainly in the ganglion cells and amacrine cells in the inner nuclear layer (INL) of the adult retina, suggesting a possible role for Id in inner retina development and in the terminal differentiation and/or maintenance of INL interneurons and ganglion cells in the adult. In this study, we used retinal progenitor cells (RPCs) from mouse embryos to study (1) the regulation of Id expression by BMPs; and (2) the effects of BMPs on retinal cell differentiation. Methods: : Expression of Id1-3 gene and protein was examined by Q-PCR and western blot respectively in retinal progenitor cell (RPC) culture prepared from E14.5 mouse embryos in the presence or absence of mouse recombinant BMP-4. Activation of Smad proteins was detected by western blot analysis in RPCs incubated with or without noggin. Id promoter activity was measured by luciferase assay. In addition, the effect of BMP-4 on the differentiation of RPCs was examined by immunohistochemistry. Results: : Significant increases of Id1-3 mRNA and protein expression levels were observed in the RPCs after treatment with BMP-4, and BMP-4 also activated the Id1 promotor to drive luciferase expression in the RPCs. A decrease in PRC proliferation accompanied these effects. Phosphorylation of Smad proteins was detected 30 min after the addition of recombinant BMP-4. These responses were abolished when cells were co-treated with noggin, a BMP antagonist. Immunoflurorescent staining demonstrated the translocation of phospho-Smad1/5/8 into the nucleus of RPC upon BMP-4 stimulation. Furthermore, BMP-4 promoted RPCs to differentiate into neuronal lineage. Conclusions: : These results demonstrate for the first time a potentially new pathway for regulating retinogenesis through the interactions between BMP-4, Ids and their downstream signaling molecules.
Persistent Identifierhttp://hdl.handle.net/10722/125813
ISSN

 

DC FieldValueLanguage
dc.contributor.authorYip, HKFen_HK
dc.contributor.authorDu, Yen_HK
dc.date.accessioned2010-10-31T11:53:23Z-
dc.date.available2010-10-31T11:53:23Z-
dc.date.issued2010en_HK
dc.identifier.citationAssociation for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, FL., 2-6 May 2010. In Investigative Ophthalmology & Visual Science, 2010, v. 51 n. 13, Abstract no. 2655en_HK
dc.identifier.issn1552-5783-
dc.identifier.urihttp://hdl.handle.net/10722/125813-
dc.description.abstractIntroduction: : Purposes: Bone morphogenetic proteins (BMPs) are multi-functional growth factors, and are well-known for regulating eye development in diverse aspects. It is also known that BMP signaling is essential for embryonic development and cellular functions such as cell growth, fate determination, differentiation and apoptosis. Inhibitors of differentiation (Id) proteins have emerged recently as the critical targets of BMPs. Id proteins are known to be important mediators of BMPs and the regulation of Id protein by BMPs is mainly through a Smad-dependent pathway. Our previous work showed that BMPs and BMPRs were co-expressed with Ids mainly in the ganglion cells and amacrine cells in the inner nuclear layer (INL) of the adult retina, suggesting a possible role for Id in inner retina development and in the terminal differentiation and/or maintenance of INL interneurons and ganglion cells in the adult. In this study, we used retinal progenitor cells (RPCs) from mouse embryos to study (1) the regulation of Id expression by BMPs; and (2) the effects of BMPs on retinal cell differentiation. Methods: : Expression of Id1-3 gene and protein was examined by Q-PCR and western blot respectively in retinal progenitor cell (RPC) culture prepared from E14.5 mouse embryos in the presence or absence of mouse recombinant BMP-4. Activation of Smad proteins was detected by western blot analysis in RPCs incubated with or without noggin. Id promoter activity was measured by luciferase assay. In addition, the effect of BMP-4 on the differentiation of RPCs was examined by immunohistochemistry. Results: : Significant increases of Id1-3 mRNA and protein expression levels were observed in the RPCs after treatment with BMP-4, and BMP-4 also activated the Id1 promotor to drive luciferase expression in the RPCs. A decrease in PRC proliferation accompanied these effects. Phosphorylation of Smad proteins was detected 30 min after the addition of recombinant BMP-4. These responses were abolished when cells were co-treated with noggin, a BMP antagonist. Immunoflurorescent staining demonstrated the translocation of phospho-Smad1/5/8 into the nucleus of RPC upon BMP-4 stimulation. Furthermore, BMP-4 promoted RPCs to differentiate into neuronal lineage. Conclusions: : These results demonstrate for the first time a potentially new pathway for regulating retinogenesis through the interactions between BMP-4, Ids and their downstream signaling molecules.-
dc.languageengen_HK
dc.publisherAssociation for Research in Vision and Ophthalmology-
dc.relation.ispartofInvestigative Ophthalmology & Visual Science-
dc.titleActivation of Id genes by BMP signaling influences proliferation and cell fate choices of retinal progenitorsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYip, HKF: hkfyip@hku.hken_HK
dc.identifier.authorityYip, HKF=rp00285en_HK
dc.identifier.hkuros176342en_HK
dc.description.otherThe 2010 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, FL., 2-6 May 2010.-

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