Role of Alternative Splicing in Sex Determination in Vertebrates

Sex Dev. 2021;15(5-6):381-391. doi: 10.1159/000519218. Epub 2021 Sep 28.

Abstract

During the process of sex determination, a germ-cell-containing undifferentiated gonad is converted into either a male or a female reproductive organ. Both the composition of sex chromosomes and the environment determine sex in vertebrates. It is assumed that transcription level regulation drives this cascade of mechanisms; however, transcription factors can alter gene expression beyond transcription initiation by controlling pre-mRNA splicing and thereby mRNA isoform production. Using the key time window in sex determination and gonad development in mice, it has been reported that new non-transcriptional events, such as alternative splicing, could play a key role in sex determination in mammals. We know the role of key regulatory factors, like WT1(+/-KTS) or FGFR2(b/c) in pre-mRNA splicing and sex determination, indicating that important steps in the vertebrate sex determination process probably operate at a post-transcriptional level. Here, we discuss the role of pre-mRNA splicing regulators in sex determination in vertebrates, focusing on the new RNA-seq data reported from mice fetal gonadal transcriptome.

Keywords: Alternative splicing; Gonad development; Isoforms; Sex determination; Vertebrates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing* / genetics
  • Animals
  • Female
  • Gonads / metabolism
  • Male
  • Mice
  • Sex Determination Processes* / genetics
  • Sex Differentiation / genetics
  • Vertebrates / genetics