Role for compartmentalization in nephron progenitor differentiation.

Aaron C Brown, Sree Deepthi Muthukrishnan, Justin A Guay, Derek C Adams, Dillon A Schafer, Jennifer L Fetting, Leif Oxburgh

Proceedings of the National Academy of Sciences of the United States of America 2013 Mar 19

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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.

Citation

Aaron C Brown, Sree Deepthi Muthukrishnan, Justin A Guay, Derek C Adams, Dillon A Schafer, Jennifer L Fetting, Leif Oxburgh. Role for compartmentalization in nephron progenitor differentiation. Proceedings of the National Academy of Sciences of the United States of America. 2013 Mar 19;110(12):4640-5