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With or without sex chromosomes, sex determination is a synthesis of many molecular events that drives a community of cells towards a coordinated tissue fate. In this review, we will consider how a sex determination pathway can be engaged and stabilized without an inherited genetic determinant. In many reptilian species, no sex chromosomes have been identified, yet a conserved network of gene expression is initiated. Recent studies propose that epigenetic regulation mediates the effects of temperature on these genes through dynamic post-transcriptional, post-translational and metabolic pathways. It is likely that there is no singular regulator of sex determination, but rather an accumulation of molecular events that shift the scales towards one fate over another until a threshold is reached sufficient to maintain and stabilize one pathway and repress the alternative pathway. Investigations into the mechanism underlying sex determination without sex chromosomes should focus on cellular processes that are frequently activated by multiple stimuli or can synthesize multiple inputs and drive a coordinated response. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’. 

In many reptiles, including the red-eared slider turtle Trachemys scripta elegans ( T. scripta ), sex is determined by ambient temperature during embryogenesis. We previously showed that the epigenetic regulator Kdm6b is elevated at the male-producing temperature and essential to activate the male pathway. In this work, we established a causal link between temperature and transcriptional regulation of Kdm6b . We show that signal transducer and activator of transcription 3 (STAT3) is phosphorylated at the warmer, female-producing temperature, binds the Kdm6b locus, and represses Kdm6b transcription, blocking the male pathway. Influx of Ca 2+ , a mediator of STAT3 phosphorylation, is elevated at the female temperature and acts as a temperature-sensitive regulator of STAT3 activation.