Role for compartmentalization in nephron progenitor differentiation

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+) comp...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 12; pp. 4640 - 4645
Main Authors:	Brown, Aaron C., Muthukrishnan, Sree Deepthi, Guay, Justin A., Adams, Derek C., Schafer, Dillon A., Fetting, Jennifer L., Oxburgh, Leif
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 19-03-2013 National Acad Sciences
Subjects:	Animals Antibodies beta Catenin - genetics beta Catenin - metabolism Biological Sciences Bone Morphogenetic Protein 7 - genetics Bone Morphogenetic Protein 7 - metabolism Cell aggregates Cell Differentiation - physiology Cell Line Cells Cellular differentiation Cultured cells Epithelial cells Epithelial Cells - cytology Epithelial Cells - metabolism Genetics Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Kidneys Mesenchymal stem cells Mice Mice, Knockout Nephrons Nephrons - cytology Nephrons - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Progenitor cells Proteins Rodents Smad Proteins - genetics Smad Proteins - metabolism Stem Cells - cytology Stem Cells - metabolism Trans-Activators - genetics Trans-Activators - metabolism Transcription Factors - genetics Transcription Factors - metabolism Tumors Viruses Wnt Proteins - genetics Wnt Proteins - metabolism Wnt Signaling Pathway - physiology
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Summary:	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.
Bibliography:	http://dx.doi.org/10.1073/pnas.1213971110 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Frank Costantini, Columbia University, New York, NY, and accepted by the Editorial Board February 7, 2013 (received for review August 27, 2012) Author contributions: A.C.B. and L.O. designed research; A.C.B., S.D.M., D.C.A., and D.A.S. performed research; J.A.G. and J.L.F. contributed new reagents/analytic tools; A.C.B. and L.O. analyzed data; and A.C.B. and L.O. wrote the paper.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.1213971110