Dataset Information

Dose-dependent nuclear ?-catenin response segregates endomesoderm along the sea star primary axis.

ABSTRACT: In many invertebrates, the nuclearization of ?-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear ?-catenin (n?-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of n?-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show that low levels of n?-catenin activity initiate bra, which is expressed in the future posterior endoderm-fated territory; intermediate levels are required for expression of foxa and gata4/5/6, which are later restricted to the endoderm; and activation of ets1 and erg in the mesoderm-fated territory requires the highest n?-catenin activity. Transcription factors acting downstream of high n?-catenin segregate the endoderm/mesoderm boundary, which is further reinforced by Delta/Notch signaling. Significantly, therefore, in sea stars, endomesoderm segregation arises through transcriptional responses to levels of n?-catenin activity. Here, we describe the first empirical evidence of a dose-dependent response to a dynamic spatiotemporal n?-catenin activity that patterns cell fates along the primary axis in an invertebrate.

SUBMITTER: McCauley BS

PROVIDER: S-EPMC4299145 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Dose-dependent nuclear β-catenin response segregates endomesoderm along the sea star primary axis.

McCauley Brenna S BS Akyar Eda E Saad H Rosa HR Hinman Veronica F VF

Development (Cambridge, England) 20150101 1

In many invertebrates, the nuclearization of β-catenin at one pole of the embryo initiates endomesoderm specification. An intriguing possibility is that a gradient of nuclear β-catenin (nβ-catenin), similar to that operating in vertebrate neural tube patterning, functions to distinguish cell fates in invertebrates. To test this hypothesis, we determined the function of nβ-catenin during the early development of the sea star, which undergoes a basal deuterostomal mode of embryogenesis. We show th ...[more]

PMID: 25516976

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Project description:BACKGROUND: Gene Regulatory Networks (GRNs) control the differentiation, specification and function of cells at the genomic level. The levels of interactions within large GRNs are of enormous depth and complexity. Details about many GRNs are emerging, but in most cases it is unknown to what extent they control a given process, i.e. the grade of completeness is uncertain. This uncertainty stems from limited experimental data, which is the main bottleneck for creating detailed dynamical models of cellular processes. Parameter estimation for each node is often infeasible for very large GRNs. We propose a method, based on random parameter estimations through Monte-Carlo simulations to measure completeness grades of GRNs. RESULTS: We developed a heuristic to assess the completeness of large GRNs, using ODE simulations under different conditions and randomly sampled parameter sets to detect parameter-invariant effects of perturbations. To test this heuristic, we constructed the first ODE model of the whole sea urchin endomesoderm GRN, one of the best studied large GRNs. We find that nearly 48% of the parameter-invariant effects correspond with experimental data, which is 65% of the expected optimal agreement obtained from a submodel for which kinetic parameters were estimated and used for simulations. Randomized versions of the model reproduce only 23.5% of the experimental data. CONCLUSION: The method described in this paper enables an evaluation of network topologies of GRNs without requiring any parameter values. The benefit of this method is exemplified in the first mathematical analysis of the complete Endomesoderm Network Model. The predictions we provide deliver candidate nodes in the network that are likely to be erroneous or miss unknown connections, which may need additional experiments to improve the network topology. This mathematical model can serve as a scaffold for detailed and more realistic models. We propose that our method can be used to assess a completeness grade of any GRN. This could be especially useful for GRNs involved in human diseases, where often the amount of connectivity is unknown and/or many genes/interactions are missing.

Dataset Information

Dose-dependent nuclear ?-catenin response segregates endomesoderm along the sea star primary axis.

Publications

Dose-dependent nuclear β-catenin response segregates endomesoderm along the sea star primary axis.

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