PUBLICATION

Cellular retinoic acid binding proteins regulate germ cell proliferation and sex determination in zebrafish

Authors
Fung, L., Dranow, D.B., Subramanian, A., Libby, N., Schilling, T.F.
ID
ZDB-PUB-241123-3
Date
2024
Source
Development (Cambridge, England)   151(24): (Journal)
Registered Authors
Schilling, Tom
Keywords
Crabp, Germ cell, Gonad development, Retinoic acid, Sex determination, Sex differentiation
MeSH Terms
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Gene Expression Regulation, Developmental
  • Female
  • Tretinoin*/metabolism
  • Germ Cells*/cytology
  • Germ Cells*/metabolism
  • Animals, Genetically Modified
  • Animals
  • Male
  • Receptors, Retinoic Acid*/genetics
  • Receptors, Retinoic Acid*/metabolism
  • Sex Determination Processes*/genetics
  • Cell Proliferation*
  • Gonads*/embryology
  • Gonads*/metabolism
  • Mutation/genetics
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
PubMed
39575928 Full text @ Development
Abstract
Cellular retinoic acid (RA) binding proteins (Crabps) solubilize intracellular RA and transport it to its nuclear receptors or cytoplasmic degradation enzymes. Despite their extreme conservation across chordates, genetic studies of Crabp function have revealed few essential functions. We have generated loss-of-function mutations in all four zebrafish Crabps and find essential roles for Crabp2s in gonad development and sex determination. Transgenic RA reporters show strong RA-responses in germ cells at the bipotential stage of gonad development. Double mutants lacking the functions of both Crabp2a and Crabp2b predominantly become male, which correlates with their smaller gonad size and reduced germ cell proliferation during gonad development at late larval and early juvenile stages. In contrast, mutants lacking the functions of both Crabp1a and Crabp1b have normal sex ratios. Exogenous RA treatments at bipotential gonad stages increase germ cell number, consistent with a direct role for RA in promoting germ cell proliferation. Our results suggest essential functions for Crabps in gonad development and sex determination.
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Human Disease / Model
Sequence Targeting Reagents
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