Zebrafish nephrogenesis involves dynamic spatiotemporal expression changes in renal progenitors and essential signals from retinoic acid and irx3b

Authors

  • Rebecca A. Wingert,

    1. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
    3. Harvard Stem Cell Institute, Cambridge, Massachusetts
    Current affiliation:
    1. Department of Biological Sciences, Galvin Life Sciences Research Building 204, University of Notre Dame, Notre Dame, IN 46556
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  • Alan J. Davidson

    Corresponding author
    1. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts
    2. Department of Medicine, Harvard Medical School, Boston, Massachusetts
    3. Harvard Stem Cell Institute, Cambridge, Massachusetts
    Current affiliation:
    1. Dr. Davidson's present address is Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1142, New Zealand
    • Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
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Abstract

Kidney nephrons are composed of proximal and distal tubule segments that perform unique roles in excretion. The developmental pathways that establish nephron segment identities from renal progenitors are poorly understood. Here, we used the zebrafish pronephros to study nephron segmentation. We found that zebrafish nephron progenitors undergo elaborate spatiotemporal expression changes of many genes before adopting a segment fate. Initially, two domains of nephron progenitors are established, then are subdivided and demarcate individual nephron segments. Using genetic and chemical genetic models of retinoic acid (RA) deficiency, we discovered that RA modulates rostral progenitor formation. To delineate downstream pathways, we knocked down the irx3b transcription factor and found it regulates proximal tubule segment size and distal segment differentiation. Our results suggest a model whereby RA patterns the early field of nephron progenitors, with subsequent factors like irx3b acting to refine later progenitor subdomains and ensure activation of segment-specific gene programs. Developmental Dynamics 240:2011–2027, 2011. © 2011 Wiley-Liss, Inc.

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