PUBLICATION

Estrogen Signaling Influences Nephron Segmentation of the Zebrafish Embryonic Kidney

Authors
Wesselman, H.M., Gatz, A.E., Pfaff, M.R., Arceri, L., Wingert, R.A.
ID
ZDB-PUB-230226-51
Date
2023
Source
Cells   12(4): (Journal)
Registered Authors
Wingert, Rebecca
Keywords
distal tubule, esr2b, estrogen, kidney, nephron, patterning, segmentation, xenoestrogen
MeSH Terms
  • Estrogens/metabolism
  • Zebrafish Proteins*/metabolism
  • Zebrafish*/genetics
  • Animals
  • Nephrons/metabolism
  • Kidney/metabolism
(all 6)
PubMed
36831333 Full text @ Cells
Abstract
Despite significant advances in understanding nephron segment patterning, many questions remain about the underlying genes and signaling pathways that orchestrate renal progenitor cell fate choices and regulate differentiation. In an effort to identify elusive regulators of nephron segmentation, our lab conducted a high-throughput drug screen using a bioactive chemical library and developing zebrafish, which are a conserved vertebrate model and particularly conducive to large-scale screening approaches. 17β-estradiol (E2), which is the dominant form of estrogen in vertebrates, was a particularly interesting hit from this screen. E2 has been extensively studied in the context of gonad development, but roles for E2 in nephron development were unknown. Here, we report that exogenous estrogen treatments affect distal tubule composition, namely, causing an increase in the distal early segment and a decrease in the neighboring distal late. These changes were noted early in development but were not due to changes in cell dynamics. Interestingly, exposure to the xenoestrogens ethinylestradiol and genistein yielded the same changes in distal segments. Further, upon treatment with an estrogen receptor 2 (Esr2) antagonist, PHTPP, we observed the opposite phenotypes. Similarly, genetic deficiency of the Esr2 analog, esr2b, revealed phenotypes consistent with that of PHTPP treatment. Inhibition of E2 signaling also resulted in decreased expression of essential distal transcription factors, irx3b and its target irx1a. These data suggest that estrogenic compounds are essential for distal segment fate during nephrogenesis in the zebrafish pronephros and expand our fundamental understanding of hormone function during kidney organogenesis.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
uab127
    		Small Deletion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    esr1MO3-esr1MRPHLNO
    esr2aMO4-esr2aMRPHLNO
    esr2bMO1-esr2bMRPHLNO
    1 - 3 of 3
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    Fish
    No data available
    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available
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    Citation
    Wesselman, H.M., Gatz, A.E., Pfaff, M.R., Arceri, L., Wingert, R.A. (2023) Estrogen Signaling Influences Nephron Segmentation of the Zebrafish Embryonic Kidney. Cells. 12(4):.