@article {65390, title = {Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b..}, journal = {Science}, volume = {368}, year = {2020}, month = {2020 Apr 17}, pages = {303-306}, abstract = {

In many reptiles, including the red-eared slider turtle (), sex is determined by ambient temperature during embryogenesis. We previously showed that the epigenetic regulator 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 We show that signal transducer and activator of transcription 3 (STAT3) is phosphorylated at the warmer, female-producing temperature, binds the locus, and represses transcription, blocking the male pathway. Influx of Ca, a mediator of STAT3 phosphorylation, is elevated at the female temperature and acts as a temperature-sensitive regulator of STAT3 activation.

}, issn = {1095-9203}, doi = {10.1126/science.aaz4165}, author = {Weber, Ceri and Zhou, Yingjie and Lee, Jong Gwan and Looger, Loren L and Qian, Guoying and Ge, Chutian and Capel, Blanche} } @article {47913, title = {A timecourse analysis of systemic and gonadal effects of temperature on sexual development of the red-eared slider turtle Trachemys scripta elegans.}, journal = {Developmental Biology}, volume = {420}, year = {2016}, month = {2016 Dec 1 }, pages = {166-77}, abstract = {

Temperature dependent sex determination (TSD) is the process by which the environmental temperature experienced during embryogenesis influences the sex of an organism, as in the red-eared slider turtle Trachemys scripta elegans. In accord with current paradigms of vertebrate sex determination, temperature is believed to exert its effects on sexual development in T. scripta entirely within the middle third of development, when the gonad is forming. However, whether temperature regulates the transcriptome in T. scripta early embryos in a manner that could influence secondary sex characteristics or establish a pro-male or pro-female environment has not been investigated. In addition, apart from a handful of candidate genes, very little is known about potential similarities between the expression cascade during TSD and the genetic cascade that drives mammalian sex determination. Here, we conducted an unbiased transcriptome-wide analysis of the effects of male- and female-promoting temperatures on the turtle embryo prior to gonad formation, and on the gonad during the temperature sensitive period. We found sexually dimorphic expression reflecting differences in steroidogenic enzymes and brain development prior to gonad formation. Within the gonad, we mapped a cascade of differential expression similar to the genetic cascade established in mammals. Using a Hidden Markov Model based clustering approach, we identified groups of genes that show heterochronic shifts between M. musculus and T. scripta. We propose a model in which multiple factors influenced by temperature accumulate during early gonadogenesis, and converge on the antagonistic regulation of aromatase to canalize sex determination near the end of the temperature sensitive window of development.

}, issn = {1095-564X}, doi = {10.1016/j.ydbio.2016.09.018}, author = {Czerwinski, Michael and Natarajan, Anirudh and Barske, Lindsey and Looger, Loren L and Capel, Blanche} } @article {6122, title = {Fine time-course expression analysis identifies cascades of activation and repression and maps a regulator of mammalian sex determination.}, journal = {PLoS Genetics}, volume = {9}, year = {2013}, month = {2013 Jul}, pages = {e1003630}, abstract = {

In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0{\textendash}E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. To elucidate the first steps of sexual fate specification, we profiled the XX and XY gonad transcriptomes at fine granularity during this period and resolved cascades of gene activation and repression. C57BL/6J (B6) XY gonads showed a consistent \ 5-hour delay in the activation of most male pathway genes and repression of female pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of the B6 strain to male-to-female sex reversal. Using this fine time course data, we predicted novel regulatory genes underlying expression QTLs (eQTLs) mapped in a previous study. To test predictions, we developed an in vitro gonad primary cell assay and optimized a lentivirus-based shRNA delivery method to silence candidate genes and quantify effects on putative targets. We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems.

}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003630}, author = {Munger, Steven C. and Natarajan, Anirudh and Looger, Loren L and Ohler, Uwe and Capel, Blanche} }