SUMMARY We have used expression profiling and in vivo imaging to characterize C. elegans embryos as they transit from a developmentally plastic state to the onset of differentiation. Normally, this transition is accompanied by activation of developmental regulators and differentiation genes, down-regulation of early-expressed genes, and large-scale re-organization of chromatin. We find that loss of plasticity and differentiation onset depends on the Polycomb complex protein mes-2/E(Z). mes-2 mutants display prolonged developmental plasticity in response to heterologous developmental regulators. Early-expressed genes remain active, differentiation genes fail to reach wild-type levels, and chromatin retains a decompacted morphology in mes-2 mutants. By contrast, loss of developmental regulators pha-4/FoxA or end-1/GATA does not prolong plasticity. This study establishes a model to analyze developmental plasticity within an intact embryo. mes-2 orchestrates large-scale changes in chromatin organization and gene expression to promote the timely loss of developmental plasticity. Our findings indicate that loss of plasticity can be uncoupled from cell fate specification.

Sox genes are indispensable for multiple aspects of development. This primer briefly describes shared properties of the Sox gene family, and five well-characterized examples of vertebrate developmental mechanisms governed by Sox gene subgroups: testis development, central nervous system neurogenesis, oligodendrocyte development, chondrogenesis, and neural crest cell development. Also featured is an interview about current issues in the field with experts

It has become increasingly evident in recent years that development is under epigenetic control. Epigenetics is the study of heritable changes in gene function that occur independently of alterations to primary DNA sequence. The best-studied epigenetic modifications are DNA methylation, and changes in chromatin structure by histone modifications, and histone exchange. An exciting, new chapter in the field is the finding that long-distance chromosomal interactions also modify gene expression. Epigenetic modifications are key regulators of important developmental events, including X-inactivation, genomic imprinting, patterning by Hox genes and neuronal development. This primer covers these aspects of epigenetics in brief, and features an interview with two epigenetic scientists. Developmental Dynamics 236: 1144 -1156, 2007.

Studies from our group and others have shown that in vitro somite myogenesis is regulated by neural tube and notochord factors including Wnt, Sonic hedgehog (Shh), and basic fibroblast growth factor (bFGF) together with transforming growth factor-beta1 (TGF-beta1). In this study we report that insulin and insulin-like growth factors I and II (IGF-I and -II) also promote myogenesis in explant cultures containing single somites or somite-sized pieces of segmental plate mesoderm from 2-day (stage 10-14) chicken embryos and that the combination of insulin/IGFs with bFGF plus TGF-beta1 promotes even higher levels of myogenesis. We also found that Shh promotes myogenesis in this in vitro system and that Shh interacts synergistically with insulin/IGFs to promote high levels of myogenesis. RT-PCR analysis detected insulin, IGF-II, insulin receptor, and IGF receptor mRNAs in both the neural tube and the somites, whereas IGF-I transcripts were detected in entire embryos but not in the neural tube or somites. Treatment of somite-neural tube cocultures with anti-insulin, anti-IGF-II, anti-insulin receptor, or anti-IGF receptor blocking antibodies caused a significant decrease in myogenesis. These results are consistent with the hypothesis that systemic IGF-I as well as insulin and IGF-II secreted by the neural tube act as additional early myogenic signals during embryogenesis. Further studies indicate that insulin, IGFs, bFGF, and Shh also stimulate somite cell proliferation and influence apoptosis.