title: The Retinal Pigment Epithelium Is a Notch Signaling Niche in the Mouse Retina.
abstract: Notch signaling in neural progenitor cell is triggered by ligands expressed in adjacent cells. To identify the sources of active Notch ligands in the mouse retina, we negatively regulated Notch ligand activity in various neighbors of retinal progenitor cells (RPCs) by eliminating mindbomb E3 ubiquitin protein ligase 1 (Mib1). Mib1-deficient retinal cells failed to induce Notch activation in intra-lineage RPCs, which prematurely differentiated into neurons; however, Mib1 in post-mitotic retinal ganglion cells was not important. Interestingly, Mib1 in the retinal pigment epithelium (RPE) also contributed to Notch activation in adjacent RPCs by supporting the localization of active Notch ligands at RPE-RPC contacts. Combining this RPE-driven Notch signaling and intra-retinal Notch signaling, we propose a model in which one RPC daughter receives extra Notch signals from the RPE to become an RPC, whereas its sister cell receives only a subthreshold level of intra-retinal Notch signal and differentiates into a neuron.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Taejeong
authors.initials: T
authors.lastname: Ha
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Kyeong Hwan
authors.initials: KH
authors.lastname: Moon
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea.
authors.forename: Le
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hatakeyama
authors.affiliation: School of Life Science and Biotechnology, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, South Korea.
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, South Korea.
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea.
authors.forename: Young-Yoon
authors.initials: YY
authors.lastname: Kong
authors.affiliation: Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimamura
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea. Electronic address: jinwookim@kaist.ac.kr.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D008024:Ligands; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000254:growth & development*; D055213:Retinal Pigment Epithelium / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D008024:Ligands; D051880:Receptors, Notch; C470629:MIB1 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Mib1; Notch signaling; RPC; RPE; mind bomb1; retina; retinal pigment epithelium; retinal progenitor cell