Emerging questions on the mechanisms and dynamics of 3D genome evolution in spiralians.

Information on how 3D genome topology emerged in animal evolution, how stable it is during development, its role in the evolution of phenotypic novelties and how exactly it affects gene expression is highly debated. So far, data to address these questions are lacking with the exception of a few key model species. Several gene regulatory mechanisms have been proposed, including scenarios where genome topology has little to no impact on gene expression, and vice versa. The ancient and diverse clade of spiralians may provide a crucial testing ground for such mechanisms. Sprialians have followed distinct evolutionary trajectories, with some clades experiencing genome expansions and/or large-scale genome rearrangements, and others undergoing genome contraction, substantially impacting their size and organisation. These changes have been associated with many phenotypic innovations in this clade. In this review, we describe how emerging genome topology data, along with functional tools, allow for testing these scenarios and discuss their predicted outcomes.

Cis-Regulatory Control of Mammalian Sex Determination.

Sex determination is the process by which an initial bipotential gonad adopts either a testicular or ovarian cell fate. The inability to properly complete this process leads to a group of developmental disorders classified as disorders of sex development (DSD). To date, dozens of genes were shown to play roles in mammalian sex determination, and mutations in these genes can cause DSD in humans or gonadal sex reversal/dysfunction in mice. However, exome sequencing currently provides genetic diagnosis for only less than half of DSD patients. This points towards a major role for the non-coding genome during sex determination. In this review, we highlight recent advances in our understanding of non-coding, cis-acting gene regulatory elements and discuss how they may control transcriptional programmes that underpin sex determination in the context of the 3-dimensional folding of chromatin. As a paradigm, we focus on the Sox9 gene, a prominent pro-male factor and one of the most extensively studied genes in gonadal cell fate determination.