Encoding regulatory state boundaries in the pregastrular oral ectoderm of the sea urchin embryo

Abstract

By gastrulation the ectodermal territories of the sea urchin embryo have developed an unexpectedly complex spatial pattern of sharply bounded regulatory states, organized orthogonally with respect to the animal/vegetal and oral/aboral axes of the embryo. Although much is known of the gene regulatory network (GRN) linkages that generate these regulatory states, the principles by which the boundaries between them are positioned and maintained have remained undiscovered. Here we determine the encoded genomic logic responsible for the boundaries of the oral aspect of the embryo that separate endoderm from ectoderm and ectoderm from neurogenic apical plate and that delineate the several further subdivisions into which the oral ectoderm per se is partitioned. Comprehensive regulatory state maps, including all spatially expressed oral ectoderm regulatory genes, were established. The circuitry at each boundary deploys specific repressors of regulatory states across the boundary, identified in this work, plus activation by broadly expressed positive regulators. These network linkages are integrated with previously established interactions on the oral/aboral axis to generate a GRN model encompassing the 2D organization of the regulatory state pattern in the pregastrular oral ectoderm of the embryo.regulatory state boundaries | pattern formation | repression circuitry B y the onset of gastrulation, bilaterian embryos consist of a complex mosaic of sharply bounded regulatory state domains, where "regulatory state" refers to the sum of specifically expressed mRNAs encoding DNA sequence-recognizing transcription factors in each nucleus. The regulatory state domains or territories are organized spatially in respect to the two major axes of the embryo, and they constitute informational specifications that determine the subsequent embryonic fates and functions of the cells descendant from these domains. Although in different modes of pregastrular embryogenesis regional specification functions are accomplished in somewhat different ways (1, 2), the end result is always the same: subdivision of the embryo into (transient) spatial regulatory states. These progressively specified regulatory states, and the boundaries between them, are the output of networks of genomically ordained interactions among regulatory genes. Gene regulatory networks (GRNs) encompass the heritable code for the embryonic development of each species. At present, the best known, experimentally determined, large-scale GRN drives the specification of endoderm and mesoderm in the embryo of the sea urchin Strongylocentrotus purpuratus up to gastrulation (3-6). This GRN model encompasses about half of the embryo, covers 30 h of development (18 h in the nonskeletogenic mesoderm), and all or almost all relevant regionally expressed regulatory genes. A recent study (7) shows that the endomesoderm GRN model contains sufficient regulatory relationships to generate a computational automaton that successfully predicts almost all spatial and temporal regulatory gene expre...

Divergence of ectodermal and mesodermal gene regulatory network linkages in early development of sea urchins

“…In euechinoids, Foxq2 sets the anterior boundary of OE by restricting the transcription of nodal in ANE (23,55). In Et, foxq2 transcripts exhibit an expression pattern consistent with observations in euechinoids and other deuterostomes, suggesting conserved roles for this gene in ANE and O-A specification ( …”

“…In euechinoids, the ectoderm is segregated into a diverse set of regulatory states defined by the future location of the stomodaeum (46,54,55). A critical factor in establishing O-A (47) polarity in sea urchins is Nodal (35,38).…”

Geometric control of ciliated band regulatory states in the sea urchin embryo

“…3 for the four subdomains of the 35 hpf CB is complete, or nearly so, with respect to the genes expressed within the various territories of the CB, except for subdomain 1. That is, mature GRNs have been published for all the territories of the embryo that border the CB, except for the apical domain through which subdomain 1 passes (Peter et al, 2012;BenTabou de-Leon et al, 2013;Li et al, 2013Li et al, , 2014. Spatial expression patterns of all the regulatory genes that are transcribed within the CB up to this time are summarized in Fig.…”

“…Remarkably, of the many genes accounted for in this expression matrix, only three are expressed throughout the extent of the CB, as is onecut, namely: z166, which is expressed in the aboral mesoderm earlier in development (supplementary material Fig. S1J) (Ransick and Davidson, 2012); otxβ1/2, which is expressed in the endoderm earlier in development (Yuh et al, 2004;Peter and Davidson, 2011); and foxg, which is expressed broadly in the oral ectoderm earlier in development (Li et al, 2014). All of the other regulators transcribed in the CB are expressed only within particular subdomains.…”

“…The various (indirect) effects of different signals and their antagonists on the disposition and breadth of the CB suggest that several different repressors might be responsible for confining its boundaries. The signals received in given territories can be expected to activate positively or negatively acting regulatory genes, but the diverse territories bordering the CB express unique regulatory states that result from different gene regulatory networks (GRNs) (Su et al, 2009;Li et al, 2012Li et al, , 2014Ben-Tabou de-Leon et al, 2013;Materna et al, 2013); consequently, regional regulatory inputs into the CB are also likely to differ. The regulatory system affecting overall CB disposition in the embryo could thus be predicted a priori to be complex.…”