Abstract
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(+) cells are refractory to WNT/β-catenin induction. We propose a model in which the primitive CITED1(+) 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis Regulatory Proteins
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Bone Morphogenetic Protein 7 / genetics
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Bone Morphogenetic Protein 7 / metabolism
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Cell Differentiation / physiology*
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Cell Line
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Epithelial Cells / cytology
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Epithelial Cells / metabolism*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Mice, Knockout
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Nephrons / cytology
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Nephrons / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Smad Proteins / genetics
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Smad Proteins / metabolism
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Stem Cells / cytology
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Stem Cells / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Wnt Proteins / genetics
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Wnt Proteins / metabolism
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Wnt Signaling Pathway / physiology*
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Apoptosis Regulatory Proteins
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Bone Morphogenetic Protein 7
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Cited1 protein, mouse
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Homeodomain Proteins
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Nuclear Proteins
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Six2 protein, mouse
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Smad Proteins
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Trans-Activators
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Transcription Factors
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Wnt Proteins
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Wnt9b protein, mouse
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beta Catenin
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bmp7 protein, mouse