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Spatiotemporal Decline of BMP Signaling Activity in Neural Progenitors Mediates Fate Transition and Safeguards Neurogenesis

Cell Rep. 2020; 
Ma TC, Vong KI, Kwan KM.
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Peptide Synthesis STAR+METHODS KEY RESOURCES TABLE REAGENT OR RESOURCE SOURCE IDENTIFIER Antibodies Rat monoclonal BrdU Abcam Cat# ab6326; RRID:AB_305426 Rabbit polyclonal CORL2 Aviva Systems Biology Cat# OAAB18965 Rabbit polyclonal FOXP2 Abcam Cat# ab16046; RRID:AB_2107107 Rabbit polyclonal LHX1 Millipore Cat# AB3200; RRID:AB_2135628 Rabbit polyclonal Nestin Genscript Cat# AD1413; RRID:AB_1720894 Rabbit monoclonal Phospho-SMAD1/5 Cell Signaling Technologies Cat# 9516S; RRID:AB_491015 Rabbit polyclonal PAX2 Thermo Fisher Scientific Cat# 71-6000; RRID:AB_2533990 Goat polyclonal OLIG2 R&D Systems Cat# AF2418; RRID:AB_2157554 Rabbit polyclonal SOX2 Millipore Cat# AB5603; RRID:AB_2286686 Rabbit polyclonal SOX9 Millipore Cat# AB5535; RRID:AB_2239761 Mouse monoclonal Tuj1 Covance Cat# MMS-435P; RRID:AB_2313773 Donkey anti-Goat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor 568 Thermo Fisher Scientific Cat# A11057; RRID:AB_2534104 Goat anti-Rabbit IgG (H+L) Highly Cross-Absorbed Secondary Antibody, Alexa Fluor 647 Thermo Fisher Scientific Cat# A21245; RRID:AB_2535813 Goat anti-Rat IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor 568 Thermo Fisher Scientific Cat# A11077; RRID:AB_2534121 Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor 488 Thermo Fisher Scientific Cat# A11029; RRID:AB_2534088 Chemicals, Peptides and Recombinant Proteins Hoechst 33342 Thermo Fisher Scientific Cat# H3570 Normal Rabbit IgG Millipore Cat# 12-370 Dynabeads M-280 Sheep Anti-Rabbit IgG Thermo Fisher Scientific Cat# 11204D Pierce Protein-G Agarose Thermo Fisher Scientific Cat# 20398 Bone Morphogenetic Protein 7 Sigma Aldrich Cat# B1434 TRIzol Reagent Invitrogen Cat# 15596-026 Bromodeoxyuridine (BrdU) Sigma-Aldrich Cat# B5002 Click-it EdU Thermo Fisher Scientific Cat# A10044 Human FGF-2 Peprotech Cat# EH-123030 Dorsomorphin dihydrochloride Abcam Cat# AB144821 SB 203580 TSAâ Plus fluorescein System RNAscope probe Mm-Gsx1 Sigma-Aldrich Cat# S8307 Perkin Elmer Cat# NEL741E001KT Advanced Cell Diagnostics Cat# 571501 Critical Commercial Assays SuperScript III First-Strand Synthesis System Thermo Fisher Scientific Cat# 18080051 Fast SYBR Green PCR Master Mix Thermo Fisher Scientific Cat# 4385612 Dual Luciferase Reporter System Promega Cat# E1960 JetPRIME Transfection Kit PolyPlus Cat# B112888 Papain Dissociation System Worthington Cat# LK003153 In Situ Cell Death Detection kit RNAscopeâ Multiplex Fluorescent Reagent Kit v2 Experimental models: Organisms/Strains Roche Cat# 11684809910 Advanced Cell Diagnostics Cat# 323100 Mouse: ICR mix Mouse: En1Cre/+ CUHK LASEC N/A Kimmel et al. Get A Quote

摘要

Neural progenitors undergo temporal fate transition to generate diversified neurons in stereotyped sequence during development. However, the molecular machineries driving progenitor fate change remain unclear. Here, using the cerebellum as a platform, we demonstrate that the temporal dynamics of a dorsoventral bone morphogenetic protein (BMP)/SMAD signaling gradient orchestrates the transition from early to late phase of neurogenesis. Initially, high BMP/SMAD activity in cerebellum neural progenitors transcriptionally represses the late-born interneuron fate determinant Gsx1. As development proceeds, gradual decline in SMAD activities from ventral to dorsal progenitors progressively alleviates suppression on Gs... More

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