Role for compartmentalization in nephron progenitor differentiation

DOI Web Site 被引用文献8件
  • Aaron C. Brown
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Sree Deepthi Muthukrishnan
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Justin A. Guay
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Derek C. Adams
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Dillon A. Schafer
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Jennifer L. Fetting
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074
  • Leif Oxburgh
    Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074

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<jats:p> Embryonic nephron progenitor cells are segregated in molecularly distinct compartments of unknown function. Our study reveals an integral role for bone morphogenetic protein-SMAD in promoting transition of progenitors from the primitive Cbp/p300-interacting transactivator 1 expressing (CITED1+) compartment to the uniquely sine oculis-related homeobox 2 expressing (SIX2-only) compartment where they become inducible by wingless-type mouse mammary tumor virus integration site family member (WNT)/β-catenin signaling. Significantly, CITED1 <jats:sup>+</jats:sup> cells are refractory to WNT/β-catenin induction. We propose a model in which the primitive CITED1 <jats:sup>+</jats:sup> compartment is refractory to induction by WNT9b/β-catenin, ensuring maintenance of undifferentiated progenitor cells for future nephrogenesis. Bone morphogenetic protein 7-SMAD is then required for transition to a distinct compartment in which cells become inducible by WNT9b/β-catenin, allowing them to progress toward epithelialization. </jats:p>

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