Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice

Pitetti, Jean-Luc, Calvel, Pierre, Romero, Yannick, Conne, Beatrice, Truong, Vy, Papaioannou, Marilena D., Schaad, Olivier, Docquier, Mylene, Herrera, Pedro Luis, Wilhelm, Dagmar and Nef, Serge (2013) Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice. PLoS Genetics, 9 1: e1003160.1-e1003160.17. doi:10.1371/journal.pgen.1003160


Author Pitetti, Jean-Luc
Calvel, Pierre
Romero, Yannick
Conne, Beatrice
Truong, Vy
Papaioannou, Marilena D.
Schaad, Olivier
Docquier, Mylene
Herrera, Pedro Luis
Wilhelm, Dagmar
Nef, Serge
Title Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
1553-7404
Publication date 2013-01
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003160
Open Access Status DOI
Volume 9
Issue 1
Start page e1003160.1
End page e1003160.17
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Abstract Mouse sex determination provides an attractive model to study how regulatory genetic networks and signaling pathways control cell specification and cell fate decisions. This study characterizes in detail the essential role played by the insulin receptor (INSR) and the IGF type I receptor (IGF1R) in adrenogenital development and primary sex determination. Constitutive ablation of insulin/IGF signaling pathway led to reduced proliferation rate of somatic progenitor cells in both XX and XY gonads prior to sex determination together with the downregulation of hundreds of genes associated with the adrenal, testicular, and ovarian genetic programs. These findings indicate that prior to sex determination somatic progenitors in Insr;Igf1r mutant gonads are not lineage primed and thus incapable of upregulating/repressing the male and female genetic programs required for cell fate restriction. In consequence, embryos lacking functional insulin/IGF signaling exhibit (i) complete agenesis of the adrenal cortex, (ii) embryonic XY gonadal sex reversal, with a delay of Sry upregulation and the subsequent failure of the testicular genetic program, and (iii) a delay in ovarian differentiation so that Insr;Igf1r mutant gonads, irrespective of genetic sex, remained in an extended undifferentiated state, before the ovarian differentiation program ultimately is initiated at around E16.5.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e1003160

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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