Early vertebrate development, differentiation and disease

During early development cells transition from a pluripotent state to progressively more differentiated states in order to generate all different tissues and organs required to construct an organism. These transitions require the coordinated regulation of many genes in a precise temporal and spatial way through interconnected Gene Regulatory Networks (GRNs). In these GRNs genes regulate each other through direct interaction of transcription factors (TFs) with cis-regulatory elements of target genes and also through protein-protein interactions. Mutations that affect protein-coding regions or their cis-regulatory elements are the cause of most human genetic diseases. Much progress has been made in recent years in uncovering the dynamic and reversible nature of epigenetic regulation. The revolution in sequencing technology has enabled genome-wide analysis of TF binding sites and histone modifications in different cell types and model organisms.


Figure 1. Chromatin state in early Xenopus embryos. Key histone modifications such as H3K4me3 (green) and H3K27me3 (red) are newly deposited in early embryos, with major increases in enrichment at blastula and gastrula stages, respectively. There is a hierarchy of active and repressive chromatin; at the blastula stage embryonic chromatin is relatively uncommitted and permissive. During gastrulation H3K27me3 is deposited on spatially regulated genes to repress multilineage gene expression. DNA methylation-dependent repression becomes prominent during organogenesis and differentiation. Embryo drawings are from Nieuwkoop and Faber (1967). From: Bogdanovic O et al. (2012). The epigenome in early vertebrate development. Genesis 50, 192-206.