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Role for compartmentalization in nephron progenitor differentiation.


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)/?-catenin signaling. Significantly, CITED1(+) cells are refractory to WNT/?-catenin induction. We propose a model in which the primitive CITED1(+) compartment is refractory to induction by WNT9b/?-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/?-catenin, allowing them to progress toward epithelialization.

SUBMITTER: Brown AC 

PROVIDER: S-EPMC3607044 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Role for compartmentalization in nephron progenitor differentiation.

Brown Aaron C AC   Muthukrishnan Sree Deepthi SD   Guay Justin A JA   Adams Derek C DC   Schafer Dillon A DA   Fetting Jennifer L JL   Oxburgh Leif L  

Proceedings of the National Academy of Sciences of the United States of America 20130304 12


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-  ...[more]

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