PUBLICATION

Ssrp1a controls organogenesis by promoting cell cycle progression and RNA synthesis

Authors
Koltowska, K., Apitz, H., Stamataki, D., Hirst, E.M., Verkade, H., Salecker, I., and Ober, E.A.
ID
ZDB-PUB-130408-7
Date
2013
Source
Development (Cambridge, England)   140(9): 1912-8 (Journal)
Registered Authors
Ober, Elke, Stamataki, Despina, Verkade, Heather
Keywords
none
MeSH Terms
  • Eye/cytology
  • Eye/embryology
  • Eye/metabolism
  • Animals
  • Transcription, Genetic*
  • Gene Expression Regulation, Developmental
  • Male
  • High Mobility Group Proteins/genetics
  • High Mobility Group Proteins/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Endoderm/cytology
  • Endoderm/embryology
  • Endoderm/metabolism
  • Cell Proliferation
  • RNA/biosynthesis
  • Transcriptional Elongation Factors/genetics
  • Transcriptional Elongation Factors/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Drosophila/embryology
  • Drosophila/genetics
  • Drosophila/metabolism
  • Cell Cycle*
  • Female
  • Organogenesis*
  • Mitotic Index
  • Chromatin Assembly and Disassembly
  • Imaginal Discs/cytology
  • Imaginal Discs/embryology
  • Imaginal Discs/metabolism
  • Drosophila Proteins/genetics
  • Drosophila Proteins/metabolism
  • DNA Replication
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Liver/cytology
  • Liver/embryology
  • Liver/metabolism
  • Mutation
(all 43)
PubMed
23515471 Full text @ Development
Abstract

Tightly controlled DNA replication and RNA transcription are essential for differentiation and tissue growth in multicellular organisms. Histone chaperones, including the FACT (facilitates chromatin transcription) complex, are central for these processes and act by mediating DNA access through nucleosome reorganisation. However, their roles in vertebrate organogenesis are poorly understood. Here, we report the identification of zebrafish mutants for the gene encoding Structure specific recognition protein 1a (Ssrp1a), which, together with Spt16, forms the FACT heterodimer. Focussing on the liver and eye, we show that zygotic Ssrp1a is essential for proliferation and differentiation during organogenesis. Specifically, gene expression indicative of progressive organ differentiation is disrupted and RNA transcription is globally reduced. Ssrp1a-deficient embryos exhibit DNA synthesis defects and prolonged S phase, uncovering a role distinct from that of Spt16, which promotes G1 phase progression. Gene deletion/replacement experiments in Drosophila show that Ssrp1b, Ssrp1a and N-terminal Ssrp1a, equivalent to the yeast homologue Pob3, can substitute Drosophila Ssrp function. These data suggest that (1) Ssrp1b does not compensate for Ssrp1a loss in the zebrafish embryo, probably owing to insufficient expression levels, and (2) despite fundamental structural differences, the mechanisms mediating DNA accessibility by FACT are conserved between yeast and metazoans. We propose that the essential functions of Ssrp1a in DNA replication and gene transcription, together with its dynamic spatiotemporal expression, ensure organ-specific differentiation and proportional growth, which are crucial for the forming embryo.

Genes / Markers
Figures
Figure Gallery (6 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rw0405bTgTransgenic Insertion
    rw0410hTgTransgenic Insertion
      s436
        Point Mutation
        s819
          Point Mutation
          s854TgTransgenic Insertion
            u428
              Point Mutation
              zdf1
                Point Mutation
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                ssrp1aMO2-ssrp1aMRPHLNO
                1 - 1 of 1
                Show
                Fish
                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                EGFPEFGEGFP
                GFPEFGGFP
                mAGFPEFGmAGFP
                mKOFP2EFGmKOFP2
                1 - 4 of 4
                Show
                Mapping
                Entity Type Entity Symbol Location
                Features819Chr: 14 Details
                GENEspon2aChr: 14 Details
                GENEssrp1aChr: 14 Details
                SSLPz9017Chr: 14 Details
                SSLPz34510Chr: 14 Details
                1 - 5 of 5
                Show