Epigenetic regulation of male fate commitment from an initially bipotential system

Abstract

A fundamental goal in biology is to understand how distinct cell types containing the same genetic information arise from a single stem cell throughout development. Sex determination is a key developmental process that requires a unidirectional commitment of an initially bipotential gonad towards either the male or female fate. This makes sex determination a unique model to study cell fate commitment and differentiation in vivo. We have focused this review on the accumulating evidence that epigenetic mechanisms contribute to the bipotential state of the fetal gonad and to the regulation of chromatin accessibility during and immediately downstream of the primary sex-determining switch that establishes the male fate.

Dissecting Cell Lineage Specification and Sex Fate Determination in Gonadal Somatic Cells Using Single-Cell Transcriptomics

“…The methylation status and chromatin accessibility of these progenitor cells have not yet been investigated. Similar to embryonic stem cells (Atlasi and Stunnenberg, 2017), it has been hypothesized that the chromatin landscape in XX and XY progenitor cells of the gonad has an open configuration that confers on these multipotent cells a unique plasticity that enables differentiation into different lineages (Garcia-Moreno et al, 2018). Following cell fate commitment and sex-specific differentiation, the chromatin landscape becomes more restricted, canalizing the developmental program toward either the male or the female fate and repressing the alternative pathway.…”

Cellular calcium and redox regulation: the mediator of vertebrate environmental sex determination?

“…Both JARID2 and JMJD3 also exhibit thermosensitive expression in the brains of sex‐reversed (neomale) Nile tilapia ( Oreochromis niloticus ) (Zhao et al ., ). The PRC2 complex is also involved in orchestrating the commitment of sexual fate in GSD species, primarily through chromatin remodeling on the sex chromosomes (Garcia‐Moreno, Plebanek & Capel, ).…”

Canonical Wnt/β-catenin activity and differential epigenetic marks direct sexually dimorphic regulation of Irx3 and Irx5 in developing mouse gonads

“…Besides canonical Wnt/β-catenin signaling, Irx3 has also been shown to be controlled by other pathways, including TGFβ (Cavodeassi et al, 2001;Gómez-Skarmeta et al, 1998), SHH (Briscoe et al, 2000;Kobayashi et al, 2002), FGF (Kobayashi et al, 2002), and retinoic acid (Sirbu et al, 2005). Notably, many of these ligands have been established as sex-specific signals that also depend on a cadre of active transcription factors and epigenetic marks within the somatic cell population during the sex differentiation window (Garcia-Moreno et al, 2018, 2019aKatoh-Fukui et al, 2012;Hiramatsu et al, 2009;Morais da Silva et al, 1996). But important questions remain: which comes first and which regulates which?…”