Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of Mammalian sex determination

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB

Item Type:Article
Title:Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of Mammalian sex determination
Creators Name:Munger, S.C. and Natarajan, A. and Looger, L.L. and Ohler, U. and Capel, B.
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-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.
Keywords:Developmental Gene Expression Regulation, Gene Expression Profiling, Gene Regulatory Networks, Gonads, LIM Domain Proteins, Ovary, Sex Determination Processes, Signal Transducing Adaptor Proteins, Small Interfering RNA, Testis, Animals, Mice
Source:PLoS Genetics
ISSN:1553-7404
Publisher:Public Library of Science (U.S.A.)
Volume:9
Number:7
Page Range:e1003630
Date:11 July 2013
Official Publication:https://doi.org/10.1371/journal.pgen.1003630
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library