Dataset Information

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

ABSTRACT: Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation.

SUBMITTER: Gouti M

PROVIDER: S-EPMC5425255 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

Gouti Mina M Delile Julien J Stamataki Despina D Wymeersch Filip J FJ Huang Yali Y Kleinjung Jens J Wilson Valerie V Briscoe James J

Developmental cell 20170427 3

Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic pert ...[more]

PMID: 28457792

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Project description:Mbodj2016 - Mesoderm specification during Drosophila development This model is described in the article: Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes. Mbodj A, Gustafson EH, Ciglar L, Junion G, Gonzalez A, Girardot C, Perrin L, Furlong EE, Thieffry D. PLoS Comput. Biol. 2016 Sep; 12(9): e1005073 Abstract: Given the complexity of developmental networks, it is often difficult to predict the effect of genetic perturbations, even within coding genes. Regulatory factors generally have pleiotropic effects, exhibit partially redundant roles, and regulate highly interconnected pathways with ample cross-talk. Here, we delineate a logical model encompassing 48 components and 82 regulatory interactions involved in mesoderm specification during Drosophila development, thereby providing a formal integration of all available genetic information from the literature. The four main tissues derived from mesoderm correspond to alternative stable states. We demonstrate that the model can predict known mutant phenotypes and use it to systematically predict the effects of over 300 new, often non-intuitive, loss- and gain-of-function mutations, and combinations thereof. We further validated several novel predictions experimentally, thereby demonstrating the robustness of model. Logical modelling can thus contribute to formally explain and predict regulatory outcomes underlying cell fate decisions. This model is hosted on BioModels Database and identified by: MODEL1607310000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

Publications

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

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