The <i>−KTS</i> splice variant of WT1 is essential for ovarian determination in mice
File(s)
Author(s)
Type
Journal Article
Abstract
Sex determination in mammals depends on the differentiation of the supporting lineage of the gonads into Sertoli or pregranulosa cells that govern testis and ovary development, respectively. Although the Y-linked testis-determining gene Sry has been identified, the ovarian-determining factor remains unknown. In this study, we identified −KTS, a major, alternatively spliced isoform of the Wilms tumor suppressor WT1, as a key determinant of female sex determination. Loss of −KTS variants blocked gonadal differentiation in mice, whereas increased expression, as found in Frasier syndrome, induced precocious differentiation of ovaries independently of their genetic sex. In XY embryos, this antagonized Sry expression, resulting in male-to-female sex reversal. Our results identify −KTS as an ovarian-determining factor and demonstrate that its time of activation is critical in gonadal sex differentiation.
Date Issued
2023-11-03
Date Acceptance
2023-09-29
Citation
Science, 2023, 382 (6670), pp.600-606
ISSN
0036-8075
Publisher
American Association for the Advancement of Science (AAAS)
Start Page
600
End Page
606
Journal / Book Title
Science
Volume
382
Issue
6670
Copyright Statement
© 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37917714
Subjects
Animals
Female
Male
Mice
Ovary
Sex Determination Processes
Sex-Determining Region Y Protein
Testis
WT1 Proteins
Protein Isoforms
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-11-02