19 Translational Control in Development

Development requires the coordinated expression of selected genes at specific times and in specific cells. Such regulated expression controls the establishment of embryonic axes, the existence of stem cells, and the specification of individual cell fates. Translational control has a key role in this regulation. It is particularly important during early embryogenesis and in the germ line, where transcription is typically quiescent; there, control of translation and mRNA stability are the primary ways to regulate patterns of protein synthesis. Yet, translational regulation continues throughout development and in somatic tissues. In this chapter, we view translational control from a developmental perspective. We discuss four major interfaces at which developmental biology meets molecular regulatory mechanisms: molecular switches, gradients, combinatorial control, and networks. These areas were chosen because they bear on fundamental processes of development. We emphasize instances in which sequence-specific regulatory factors control particular mRNAs, and we do not cover the role of general translation factors (e.g., eIF4E and eIF2α) on growth and differentiation (Chapter 4). MECHANISMS OF TRANSLATIONAL CONTROL: A PRIMER Translation is a multistep process and can be divided into three phases: initiation, elongation, and termination. In principle, translational control can be exerted in any of these phases. We focus in this chapter on initiation, which appears to be the most common point of control during development. Translational initiation involves more than 20 proteins, multiple biochemical complexes, and a series of separable steps (Chapter 4). A complex containing eukaryotic initiation factor 4E (eIF4E) (cap-binding protein) and eIF4G is crucial. At...