<i>Sall4</i> regulates posterior trunk mesoderm development by promoting mesodermal gene expression and repressing neural genes in the mesoderm

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  • Matthew P. Pappas
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA
  • Hiroko Kawakami
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA
  • Dylan Corcoran
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA
  • Katherine Q. Chen
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA
  • Earl Parker Scott
    University of Minnesota 4 Department of Neuroscience , , Minneapolis, MN 55455 , USA
  • Julia Wong
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA
  • Micah D. Gearhart
    Developmental Biology Center, University of Minnesota 3 , Minneapolis, MN 55455 , USA
  • Ryuichi Nishinakamura
    Institute of Molecular Embryology and Genetics, Kumamoto University 6 Department of Kidney Development , , Kumamoto 860-0811 , Japan
  • Yasushi Nakagawa
    Stem Cell Institute, University of Minnesota 2 , Minneapolis, MN 55455 , USA
  • Yasuhiko Kawakami
    University of Minnesota 1 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA

説明

<jats:title>ABSTRACT</jats:title> <jats:p>The trunk axial skeleton develops from paraxial mesoderm cells. Our recent study demonstrated that conditional knockout of the stem cell factor Sall4 in mice by TCre caused tail truncation and a disorganized axial skeleton posterior to the lumbar level. Based on this phenotype, we hypothesized that, in addition to the previously reported role of Sall4 in neuromesodermal progenitors, Sall4 is involved in the development of the paraxial mesoderm tissue. Analysis of gene expression and SALL4 binding suggests that Sall4 directly or indirectly regulates genes involved in presomitic mesoderm differentiation, somite formation and somite differentiation. Furthermore, ATAC-seq in TCre; Sall4 mutant posterior trunk mesoderm shows that Sall4 knockout reduces chromatin accessibility. We found that Sall4-dependent open chromatin status drives activation and repression of WNT signaling activators and repressors, respectively, to promote WNT signaling. Moreover, footprinting analysis of ATAC-seq data suggests that Sall4-dependent chromatin accessibility facilitates CTCF binding, which contributes to the repression of neural genes within the mesoderm. This study unveils multiple mechanisms by which Sall4 regulates paraxial mesoderm development by directing activation of mesodermal genes and repression of neural genes.</jats:p>

収録刊行物

  • Development

    Development 151 (5), dev202649-, 2024-03-01

    The Company of Biologists

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