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Published on: July 30, 2015
Cellular retinoic acid-binding proteins regulate germ cell proliferation and sex determination in zebrafish
Lianna Fung1, Daniel B Dranow1, Arul Subramanian1
1Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
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 Crabp2 proteins 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.
Insights
Cellular retinoic acid-binding proteins (Crabps) are crucial for zebrafish gonad development and sex determination. Loss of Crabp2 function leads to male development, highlighting their essential roles.
Area of Science:
- Developmental Biology
- Genetics
- Endocrinology
Background:
- Cellular retinoic acid-binding proteins (Crabps) are conserved proteins involved in retinoic acid (RA) transport.
- Previous genetic studies have identified limited essential functions for Crabps.
- Zebrafish offer a powerful model for studying conserved developmental processes.
Purpose of the Study:
- To investigate the essential functions of all four zebrafish Crabp genes in development.
- To determine the role of Crabps in gonad development and sex determination.
- To elucidate the involvement of RA signaling in germ cell proliferation and gonadogenesis.
Main Methods:
- Generation of loss-of-function mutations in all four zebrafish Crabp genes (Crabp1a, Crabp1b, Crabp2a, Crabp2b).
- Utilized transgenic RA reporters to visualize RA activity in developing gonads.
- Analyzed gonad morphology, germ cell number, and sex ratios in mutant zebrafish.
- Administered exogenous RA treatments to assess its impact on germ cell proliferation.
Main Results:
- Loss-of-function mutations in Crabp2a and Crabp2b resulted in predominantly male zebrafish with smaller gonads and reduced germ cell proliferation.
- Mutations in Crabp1a and Crabp1b did not affect sex ratios.
- RA signaling was detected in germ cells during the bipotential gonad stage.
- Exogenous RA treatment increased germ cell numbers, confirming RA's role in proliferation.
Conclusions:
- Zebrafish Crabp2 proteins play essential roles in gonad development and sex determination.
- RA signaling is critical for promoting germ cell proliferation during early gonadogenesis.
- Crabps are vital regulators of RA homeostasis during vertebrate reproductive development.
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