A gene regulatory network controlling the embryonic specification of
endoderm
Nature 474, 7353 (2011). doi:10.1038/nature10100
Authors: Isabelle S. Peter & Eric H. Davidson
Specification of endoderm is the prerequisite for gut formation in the
embryogenesis of bilaterian organisms. Modern lineage labelling studies have shown that in the sea urchin embryo model system, descendants
of the veg1 and veg2 cell lineages produce the endoderm, and that the veg2
lineage also gives rise to mesodermal cell types. It is known that Wnt/β-catenin
signalling is required for endoderm specification and
Delta/Notch signalling is required for mesoderm specification.
Some direct cis-regulatory targets of these signals have been found and various phenomenological patterns of gene expression have
been observed in the pre-gastrular endomesoderm. However, no comprehensive,
causal explanation of endoderm specification has been conceived for sea urchins,
nor for any other deuterostome. Here we propose a model, on the basis of the
underlying genomic control system, that provides such an explanation, built
at several levels of biological organization. The hardwired core of the control
system consists of the cis-regulatory apparatus of endodermal regulatory
genes, which determine the relationship between the inputs to which these
genes are exposed and their outputs. The architecture of the network circuitry
controlling the dynamic process of endoderm specification then explains, at
the system level, a sequence of developmental logic operations, which generate
the biological process. The control system initiates non-interacting endodermal
and mesodermal gene regulatory networks in veg2-derived cells and extinguishes
the endodermal gene regulatory network in mesodermal precursors. It also generates
a cross-regulatory network that specifies future anterior endoderm in veg2
descendants and institutes a distinct network specifying posterior endoderm
in veg1-derived cells. The network model provides an explanatory framework
that relates endoderm specification to the genomic regulatory code.
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