Analysis of the Embryonic Pituitary Transcriptome in Mice with Conditional Deletion of the Forkhead Box Transcription Factor, Foxo1

Presentation Number: SUN 267
Date of Presentation: April 2nd, 2017

Jyoti Kapali*, Matt Geisler and Buffy Sue Ellsworth
Southern Illinois University Carbondale, Carbondale, IL

Abstract

FOXO1 is expressed in a number of tissues and regulates processes such as insulin signaling, apoptosis and oxidative stress with critical roles during embryonic development. Our previous studies show that pituitary-specific deletion of Foxo1 (Foxo1Dpit) in mice results in delayed terminal differentiation of the growth hormone (GH) producing cell type, the somatotrope. To identify molecules that mediate the ability of FOXO1 to promote terminal differentiation of somatotropes, we undertook a transcriptome-wide RNA sequencing approach to analyze developing (e16.5) pituitary of wildtype and Foxo1Dpit mice . Wildtype and Foxo1Dpit pituitary glands were sequenced by Illumina at a depth of approximately 41-57 million reads per sample which were aligned and mapped to a mouse reference genome on CLC workbench. The reads generated were analyzed to determine differentially expressed genes using the DESeq2 package in R/Bioconductor. We identified genes that were differentially regulated (FDR corrected p-value <0.05) when Foxo1Dpit mice were compared to wild-type animals. DAVID (Bioinformatics Resources 6.8) analysis of those 69 genes revealed that 35 of those genes have molecular functions such as signal transduction, transcriptional regulation, protein kinase activity, cellular response to insulin stimulus, and apoptosis. Several genes including Doc2b, Fam46c, and Rassf4 were confirmed as differentially expressed by RT-qPCR. Together these data suggest that FOXO1 promotes somatotrope differentiation by regulating genes involved in a number of cell processes including signal transduction.

 

Nothing to Disclose: JK, MG, BSE