7 - Mouse models to identify genes throughout oogenesis

Summary

Introduction

In mammals, oocytes initially develop from primordial germ cells (PGCs), which divide and migrate to the gonad to become oogonia during fetal development. At birth, a mammalian female contains about two million primary oocytes, which remain quiescent in the prophase of meiosis I (refer to Chapters 2 and 6). Eventually, a subset of these immature oocytes will be surrounded by granulosa cells to form the primordial follicle pool. Folliculogenesis begins with the activation of a primordial follicle and ends with either the release of a fertilizable oocyte or follicular atresia. The pathways involved in oogenesis and folliculogenesis have been extensively studied, with an attempt to better understand the molecular mechanisms underlying successful ovulation and fertilization. In this chapter, we highlight three major pathways critical for female germ cell development – transforming growth factor beta (TGFβ), phosphatidylinositol 3-kinase (PI3K), and small RNAs – and discuss mouse models used for dissecting the function of genes involved in these pathways.

Overview of the TGFβ pathway

The TGFβ superfamily is the largest family of secreted proteins in mammals [1]. Members of the TGFβ family are involved in a variety of developmental and physiological processes. The canonical TGFβ signaling pathway begins with two dimeric ligands binding to type I and type II receptors to form an activated heterotetrameric receptor complex. The type II receptor within this activated complex phosphorylates the type I receptor, which in turn phosphorylates downstream SMAD proteins. These phosphorylated, receptor-regulated SMAD (R-SMAD) proteins can then bind to the common SMAD (co-SMAD; i.e., SMAD4), translocate into the nucleus, and interact with SMAD binding partners to regulate transcription of target genes (Figure 7.1).