  Dmrt1 is pivotal in testis formation and function by interacting with genes
crucial for Sertoli cell differentiation, such as Sox9. It represses
female-determining pathways and ovarian formation by silencing Foxl2. Across
127 vertebrate species, Dmrt1 exhibits sexually dimorphic expression, prior to
and during gonadal sex differentiation and in adult testes, implicating its
role in master regulation of sex determination and gonadal sex differentiation.
Dmrt1 emerges as a master sex-determining gene in one fish, frog, chicken and
reptile. Recent studies suggest epigenetic regulation of Dmrt1 in its promoter
methylation and transposable element insertion introducing epigenetic
modification to cis-regulatory elements, alongside non-coding RNA involvement,
in a wide spectrum of sex-determining mechanisms. Additionally, alternative
splicing of Dmrt1 was found in all vertebrate groups except amphibians. Dmrt1
has evolved many lineage-specific isoforms (ranging from 2 to 10) but has no
sex-specific splicing variants in any taxa, which is in sharp contrast to the
constitutional sex-specific splicing of Dsx in insects. Future research should
focus on understanding the molecular basis of environmental sex determination
from a broader taxon, and the molecular basis of epigenetic regulation. It is
also essential to understand why and how multiple alternative splicing variants
of Dmrt1 evolve and the specific roles each isoform plays in sex determination
and gonadal sex differentiation, as well as the significant differences in the
molecular mechanisms and functions of alternative splicing between Dmrt1 in
vertebrates and sex-specific splicing of Dsx in insects. Understanding the
differences could provide deeper insights into the evolution of sex-determining
mechanisms between vertebrates and insects.
