A missing link in the sea urchin embryo gene regulatory network:
            <i>hesC</i>
            and the double-negative specification of micromeres

Revilla-i-Domingo, Roger; Oliveri, Paola; Davidson, Eric H.

doi:10.1073/pnas.0705324104

Cited by 136 publications

(185 citation statements)

References 34 publications

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“…In the Sp GRN, the skeletogenic regulatory state is installed in micromeres by specific repression of the repressive hesC gene, executed by the micromere-specific repressor Pmar1, thus opening the double-negative gate subcircuit. HesC is transcriptionally expressed throughout the whole Sp embryo, except where this gene is turned off by pmar1 expression in the micromeres; thus, in Sp, hesC transcription and skeletogenic function are Boolean exclusives (4,24,31). However, in Et, hesC is expressed in micromeres at the same time as are ets1 and delta (by 10 h), in direct contrast to its double-negative gate function in Sp.…”

Section: Resultsmentioning

confidence: 83%

“…delta. The euechinoid delta gene is also an immediate transcriptional activation target of the Sp micromere double-negative gate subcircuit, and it continues to be expressed in this lineage until blastula stage, when its expression is extinguished there and instead appears in the surrounding nonskeletogenic mesoderm cells (24,29,30). In Et, delta expression occurs early in micromeres, 4-6 h before that of alx1, suggesting a primary function unconnected to later skeletogenic specification (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…tbr. Finally, the tbr gene, which is required for and coopted to skeletogenic function in euechinoids (22,24,32,33), is again expressed very differently in Et. Although the tbr gene is first activated in the micromeres, its expression quickly spreads to the entire nonskeletogenic mesodermal domain, where by double in situ hybridization, it can be seen to totally overlap that of ets1, and, in direct contrast to Sp, there is no evidence from its expression pattern that it ever plays a skeletogenic role.…”

Section: Resultsmentioning

confidence: 99%

“…The alx1 gene is a primary driver of skeletogenic specification and differentiation in sea urchin embryo and adult development, and it is a member of a family of homeodomain genes also used in vertebrate skeletogenesis (22,(25)(26)(27). In euechinoids alx1 is one of the initial set of positively acting transcriptional regulators that set up the skeletogenic regulatory state, and it is transcriptionally activated by a double-negative derepression subcircuit (24,28), immediately upon segregation of the skeletogenic micromere founder cells early in cleavage (25). In Sp, this gene then participates in direct cross-regulation of the succeeding tiers of the skeletogenic specification GRN.…”

Section: Resultsmentioning

confidence: 99%

“…A dramatic demonstration of the function of the skeletogenic double-negative gate in Sp is afforded by either overexpression of the repressor Pmar1 or introduction into the egg of hesC morpholino antisense oligonucleotide (MASO), either of which results in global transformation of embryonic cells to skeletogenic fate, and in global expression of the double-negative target genes delta, alx1, and tbr (4,24,28,31,32). In Fig.…”

Section: Experimental Tests For Specific Linkages Of the Euechinoid Smentioning

confidence: 99%

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Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses

Erkenbrack

Davidson

2015

Proc. Natl. Acad. Sci. U.S.A.

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Evolution of animal body plans occurs with changes in the encoded genomic programs that direct development, by alterations in the structure of encoded developmental gene-regulatory networks (GRNs). However, study of this most fundamental of evolutionary processes requires experimentally tractable, phylogenetically divergent organisms that differ morphologically while belonging to the same monophyletic clade, plus knowledge of the relevant GRNs operating in at least one of the species. These conditions are met in the divergent embryogenesis of the two extant, morphologically distinct, echinoid (sea urchin) subclasses, Euechinoidea and Cidaroidea, which diverged from a common late Paleozoic ancestor. Here we focus on striking differences in the mode of embryonic skeletogenesis in a euechinoid, the well-known model Strongylocentrotus purpuratus (Sp), vs. the cidaroid Eucidaris tribuloides (Et). At the level of descriptive embryology, skeletogenesis in Sp and Et has long been known to occur by distinct means. The complete GRN controlling this process is known for Sp. We carried out targeted functional analyses on Et skeletogenesis to identify the presence, or demonstrate the absence, of specific regulatory linkages and subcircuits key to the operation of the Sp skeletogenic GRN. Remarkably, most of the canonical design features of the Sp skeletogenic GRN that we examined are either missing or operate differently in Et. This work directly implies a dramatic reorganization of genomic regulatory circuitry concomitant with the divergence of the euechinoids, which began before the end-Permian extinction.GRN evolution | network linkages | embryonic skeletogenesis | sea urchin embryogenesis T he mechanisms responsible for evolutionary divergence of animal body plans, as so extensively documented in the Phanerozoic fossil record, lie in alterations of the encoded genomic regulatory programs that direct development. This principle has long been evident a priori (1), and overwhelmingly, accumulating current evidence precludes any other general explanation (2). However, it still remains a challenge to adduce specific examples in which evolutionary rewiring of developmental gene-regulatory networks (GRNs) can be seen to account for observed differences in morphogenetic processes that distinguish descendants of a common ancestor. Knowledge of developmental GRNs remains insufficiently extensive, and it is not trivial to locate useful examples, which require comparison within a monophyletic clade at just sufficient distance so that the diverged morphology is clearly the output of homologous networks of developmental regulatory gene interactions.In recent years, largely complete developmental GRN models have been solved that causally explain spatial specification in large domains of the embryo of the sea urchin Strongylocentrotus purpuratus (Sp), up to gastrulation (3-5). The explanatory power of these networks was demonstrated, in these pages, by a predictive computational analysis that showed that they contain sufficient informat...

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Experimental Tests For Specific Linkages Of the Euechinoid Smentioning

confidence: 99%

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Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses

Erkenbrack

Davidson

2015

Proc. Natl. Acad. Sci. U.S.A.

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Sea Urchin Embryo: Specification of Cell Fates

Angerer

2012

Encyclopedia of Life Sciences

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Specification of cell fate in sea urchin embryos involves initial asymmetric distribution of maternal molecules that establish posterior and anterior domains of transcription activity. Subsequently, fates of most blastomeres along the anterior–posterior and dorsal–ventral axes of the embryo are patterned by cell–cell interactions involving signalling ligands and cell surface receptors. These signalling pathways regulate the operation of networks of genes encoding transcription factors and additional signals, which guide the terminal differentiation of different cell types. Most of the signalling mechanisms that establish different embryonic territories and some of the transcription factors that specify cell types are highly conserved with those that pattern vertebrate embryos. The relative simplicity of the sea urchin embryo and the existence of tools for rapidly determining gene function provide clear advantages for understanding how early developmental processes work. Key Concepts: Sea urchin embryogenesis employs the two common mechanisms of early fate specification, inheritance of maternal molecules and signalling among cells. The maternally derived initial state, in the absence of all known signals sent among the cells of the embryo, promotes development of anterior neuroectoderm, a region of ectoderm within which nerves develop. Early posterior canonical Wnt signalling activates transcription factors followed by additional signals that convert posterior blastomeres to mesoderm and endoderm and restrict the anterior neuroectoderm fate to the anterior end of the embryo. Patterning of anterior (neuroectoderm) and posterior (endomesoderm) fates requires mutual antagonism between the gene regulatory networks headed by Wnt and Six3, respectively. Nodal signalling is necessary and sufficient for specification of fates along the dorsal–ventral axis, including oral and aboral ectoderm types. Anterior–posterior (AP) and dorsal–ventral (DV) patterning are interconnected and temporally coordinated because early posterior canonical Wnt signalling is required to derepress nodal expression. The components of the major tissue territory gene regulatory networks (GRNs) have been identified by studying embryos lacking signalling through canonical Wnt, Nodal or BMP, and their functional relationships determined by knocking down each of the corresponding proteins in vivo with morpholino oligonucleotides and monitoring effects on expression of other genes. Individual cell types in sea urchin embryos are determined when their fates cannot be changed experimentally; this process requires stable activation of genes necessary for specification of a particular cell type and stable repression of those required for specification of other cell types. The GRN devices that produce stable regulatory states are reinforcing cross‐regulatory and feedback loops among the component transcription factors, which render these states insensitive to signals. The sea urchin embryo has enormous capacity before larval stages to change cell fates upon experimental challenge because the fates of many cells are only gradually specified and can be altered by signals sent from other cells.

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Ingression of primary mesenchyme cells of the sea urchin embryo: A precisely timed epithelial mesenchymal transition

Ferkowicz

McClay

2007

Birth Defects Research Pt C

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Epithelial-mesenchyme transitions (EMTs) are familiar to all scholars of development. Each animal system utilizes an EMT to produce mesenchyme cells. In vertebrates, for example, there are a number of EMTs that shape the embryo. Early, entry of epiblast cells into the primitive streak is followed by the emergence of mesoderm via an EMT process. The departure of neural crest cells from the margin of the neural folds is an EMT process, and the delamination of cells from the endomesoderm to form the supporting mesenchyme of the lung, liver, and pancreas are EMTs. EMTs are observed in Drosophila following invagination of the ventral furrow, and even in Cnidarians, which have only two germ layers, yet mesoglial and stem cells delaminate from the epithelia and occupy the matrix between the ectoderm and endoderm. This review will focus on a classic example of an EMT, which occurs in the sea urchin embryo. The primary mesenchyme cells (PMCs) ingress from the vegetal plate of this embryo precociously and in advance of archenteron invagination. Because ingression is precisely timed, the PMC lineage precisely known, and the embryo easily observed and manipulated, much has been learned about how the ingression of PMCs works in the sea urchin. Though the focus of this review is the sea urchin PMCs, there is evidence that all EMTs share many common features at both cellular and molecular levels, and many of these mechanisms are also shown to be involved in tumor progression, especially metastasizing carcinomas.

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A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres

Cited by 136 publications

References 34 publications

Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses

Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses

Sea Urchin Embryo: Specification of Cell Fates

Ingression of primary mesenchyme cells of the sea urchin embryo: A precisely timed epithelial mesenchymal transition

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