Biology Reference
In-Depth Information
Transcription factors, and even more so signaling mole-
cules, are almost always used repeatedly during develop-
ment. Their function, though, is always specific to the
developmental context, and the sets of target genes they
control depend on the presence of other transcription
factors with which they combine to regulate gene expres-
sion. In the end, the overall developmental control system is
directly dependent on regulatory genomic DNA sequence.
From early embryogenesis to adult body plan, the regula-
tory genome defines the spatial and temporal organization
of development.
encoded in genomic DNA, any model of a GRN has to be
organized from the perspective of the genome.
Figure 11.2
shows a GRN model produced in the BioTapestry platform
[11,12]
. The process modeled here is the specification of
endomesoderm in the first 30 h of sea urchin embryo
development
15]
. The BioTapestry platform is
designed to represent all biological entities that constitute
GRNs. The components of GRNs and the symbolism used
to represent them in BioTapestry are as follows:
Regulatory factors: At each node of the GRN the gene
is indicated by a horizontal bar and an arrow, the arrow
representing the protein-coding sequence and the ultimate
protein product, i.e., the regulatory factor. These sequence-
specific DNA-binding molecules are the moving parts
(literally diffusing within the nucleus) of GRNs. The
physical regulatory linkage is shown in the BioTapestry
GRN model by a line emanating from the arrow at the gene
encoding the regulatory factor.
Cis-regulatory sequences: The horizontal bar of each
network node in the BioTapestry model specifically
represents the cis-regulatory sequence of the respective
[13
e
GRN STRUCTURAL COMPONENTS
AND MODEL REPRESENTATION
It is a great challenge for the mind to zoom out from
transcriptional control of a single regulatory gene to the
flow of regulatory information encoded in GRNs. To enable
this shift in perception, adequate system level models are
essential. Since the architecture of GRNs is directly
FIGURE 11.2
The GRN underlying pregastrular specification of mesodermal and endodermal domains of the sea urchin embryo. The network
shows explicitly the regulatory interactions that underlie specification of the skeletogenic, mesodermal and endodermal domains of the sea urchin embryo
(Strongylocentrotus purpuratus) up to the time when it gastrulates. By this point, entirely separate GRNs are in operation in each of these regions. All genes
included in these GRNs encode transcription factors, or in a few cases signaling ligands or receptors, except for the samples of effector genes shown in the
small rectangles at the bottom of the figure. The regulatory inputs into each gene, and the outputs from it to other genes, are indicated. Time runs
approximately from top to bottom, and the GRNs portrayed include all linkages active at any point in the interval from very early cleavage to the onset of
gastrulation. The large colored panels represent, from left to right, the GRN for specification of the skeletogenic lineage ('PMC'); the GRNs for speci-
fication of oral (top) and aboral (middle) mesoderm ('oral NSM' and 'aboral NSM'); the GRN for specification of anterior (future foregut) endoderm ('Veg2
endoderm'); and the GRN for specification of future posterior (hindgut) endoderm ('Veg1 endoderm'). A recent version of this continuously updated
network model built in the BioTapesty computational platform is shown; for current status, see (
http://sugp.caltech.edu/endomes/#BioTapestryViewer
)
.
