title: Notch activity is downregulated just prior to retinal ganglion cell differentiation.
abstract: The Notch signaling pathway is important at several stages of retinal development including the differentiation of retinal ganglion cells and Muller glia. The downstream effectors of Notch signaling, Hes1 and Hes5, have been shown to be critical in the retina as well. While Notch activity directly regulates Hes1 and Hes5 elsewhere in the nervous system, it has been unclear whether Hes1 and/or Hes5 are directly regulated by Notch activity in the developing retina. Here, we report that both Hes1 and Hes5 are directly regulated by Notch activity during retinal development. Using fluorescence-based Hes1 and Hes5 reporter constructs, we can monitor Notch activity in progenitor cells in the intact retina, and we find that Notch activity is downregulated just prior to retinal ganglion cell differentiation.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: Branden R
authors.initials: BR
authors.lastname: Nelson
authors.forename: Burak
authors.initials: B
authors.lastname: Gumuscu
authors.forename: Byron H
authors.initials: BH
authors.lastname: Hartman
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Reh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002642:Chick Embryo; D017124:Conserved Sequence / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005136:Eye Proteins; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse