title: miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability.
abstract: The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associated with a thickened neuroepithelium. The neuroepithelium shows increased progenitor proliferation, decreased cell death, and precocious neuronal differentiation. mRNA profiling at multiple time points during neurulation uncovers a complex pattern of changing targets over time. Overexpression of one of these targets, Fgf15, in the neuroepithelium of the chick embryo induces precocious neuronal differentiation. Compound mutants between mir-302 and the related mir-290 locus have a synthetic lethal phenotype prior to neurulation. Our results show that mir-302 helps regulate neurulation by suppressing neural progenitor expansion and precocious differentiation. Furthermore, these results uncover redundant roles for mir-290 and mir-302 early in development.
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Parchem
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Moore
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fish
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jacqueline G
authors.initials: JG
authors.lastname: Parchem
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Tarcio T
authors.initials: TT
authors.lastname: Braga
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Shenoy
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Oldham
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Schneider
authors.affiliation: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: robert.blelloch@ucsf.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002642:Chick Embryo; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology*
chemical_list: C558265:MIRN302 microRNA, mouse; D035683:MicroRNAs