CtBP Proteins in Vertebrate Development

Abstract

The fundamental question facing developmental biology is how the diversity of cell and tissue types that comprise a vertebrate organism can be generated from a single fertilized egg. A critical aspect of the developmental process is setting up and maintaining the differential gene expression that is required to establish the variety of cell lineages present in the adult organism. Thus, an important aspect of understanding development is understanding how early asymmetries in the transcriptome of various cell types are established and, once established, how they are maintained or modified through subsequent generations and differentiation events. This process is carried out by the combined activities of both sequence specific DNA binding factors and their associated coactivators and compressors that act on either the general transcriptional machinery or the histone component of chromatin. CtBP proteins comprise one branch of corepressors that get recruited to DNA via sequence-specific DNA binding proteins and regulate gene expression. In mice, the CtBP family proteins are encoded by two loci, Ctbp1 and Ctbp2. The transcripts encoding the CtBP1 and CtBP2 proteins are widely expressed and exhibit both unique and shared expression domains in the developing embryo. Genetic analysis of mice harboring mutations in Ctbp1 and Ctbp2 indicate that the proteins they encode likely have redundant functions during embryogenesis but are differentially required for specific developmental processes. This analysis shows that CtBP proteins are important in the formation of the placenta and tissues derived from all three germ layers, including muscles, skin, neural ectoderm, and intestinal epithelium. This chapter focuses on the roles of CtBPl and CtBP2 proteins in vertebrate development, with an emphasis on the genetics of Ctbp1 and Ctbp2, the possible pathways that utilize CtBP proteins during embryogenesis, and the evidence that CtBP proteins could be implicated in multiple developmental processes linked to human diseases.