Systems Biology of Embryogenesis
Genomics approaches have contributed substantially to the study of early embryogenesis and development – from the level of transcriptional regulation to cellular differentiation and patterning. We now know that embryonic development is network-based and involves dynamic interactions between transcription factors and epigenetic states of chromatin. Our goals are to address the following major issues in development.
Paraiso et al published in Cell Reports, 2019: Endodermal maternal transcription factors establish super enhancers during zygotic genome activation.
Maternal transcription factors function at the top of the regulatory hierarchy to specify the primary germ layers at the onset of zygotic genome activation. We focus on the formation of endoderm progenitor cells and examine the interactions between maternal transcription factors and epigenetic changes underlying the cell specification process. Endoderm-specific factors Otx1 and Vegt together with Foxh1 orchestrate endoderm formation by coordinated binding to select cis-regulatory motifs. These interactions occur before the deposition of enhancer epigenetic marks around the cis-regulatory motifs, and establish super enhancers associated with important endodermal genes. Therefore, maternal transcription factors Otx1, Vegt and Foxh1 combinatorially regulate the activity of super enhancers, which in turn activate key lineage-specifying genes during ZGA.
Featured article in Matters Arising: Paraiso et al., Developmental Cell, 2019: Morpholinos do not elicit an innate immune response during early Xenopus embryogenesis.
Gene expression interference by morpholinos has been questioned because of unwanted side effects, including immune response induction by a limited set of morpholinos. By performing a meta-analysis of available transcriptomic datasets, Paraiso et al. show that induction of an immune response is not a general side effect of morpholinos during early embryogenesis.