Establishing the role of Pea3, an ETS family transcription factor, during mouse embryonic development

Abstract

<p>PEA3 is an ETS family transcription factor and the founding member of the PEA3 group which consists of two other PEA3 related proteins, ERM and ER81. They share ~95% amino acid identity within their DNA binding domains and ~50% a.a. identity outside of this region. The goal of this study was to identify the role of PEA3 during mouse embryogenesis. In order to achieve this objective, two complementary approaches were employed. Firstly, the embryonic expression pattern of PEA3 was determined by the whole mount in-situ hybridization from mid-gastrulation through early organogenesis. The Pea3 mRNA was detected in tissues derived from all three germ layers. The sites of expression correlated with regions of embryonic induction, a process governing tissue differentiation, morphogenesis and organogenesis. This study revealed that PEA3 was expressed during gastrulation, patterning of the CNS, neural differentiation, craniofacial development, muscle development, kidney development and limb development. Secondly, we employed a gene knock-out strategy to define the essential functions of PEA3 either during embryogenesis and within the adult mouse. Pea3 proved dispensable for embyogenesis. Expression analysis of both ERM and ER81 revealed that ERM may have provided redundant functions in Pea3 null embryos. However, the male null mice were infertile. Furthermore, female null mice exhibited vastly reduced arbortization of the ductal tree within the developing mammary gland. Hence, this study revealed that PEA3 was required for male fertility and ductal morphogenesis of the mammary gland.</p>