title: Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors.
abstract: Notch signaling is critical for multiple aspects of neurogenesis, but how it regulates the proliferation and differentiation of neural stem cells (NSCs) and intermediate neural progenitors (INPs) has not been well elucidated, especially in vivo. In this study, we conditionally ablated the transcription factor RBP-J, which mediates signaling from all four mammalian Notch receptors, in the basal forebrain and ventral midbrain using the RBP-J-floxed mouse and a newly established Nestin-Cre mouse. We found that at early stage of neurogenesis (E11.5), the frequency of neurospheres increased significantly in the RBP-J-inactivated regions. The majority of the RBP-J deficient neurospheres were composed of INPs, suggesting the precocious differentiation of NSCs into INPs. Meanwhile, neuronal differentiation was reduced in the same regions at E11.5, inconsistent with the precocious differentiation phenotype in most Notch-related mutants. At late neurogenic stages (E17.5 and neonatal), as expected from precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the RBP-J-ablated regions, accompanied by a significant increase of both neurons and glial cells. These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCs into INPs and support the generation of certain early born neurons at early neurogenic stages.
authors.affiliation: Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Chang-Le Xi Street #17, Xian 710032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zheng
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Liu
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Zheng-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qin
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D019076:Transgenes
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C497571:Rbpj protein, mouse; D051880:Receptors, Notch