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

• Published in: Developmental cell Vol. 41; no. 3; pp. 243 - 261.e7
• Main Authors: Gouti, Mina, Delile, Julien, Stamataki, Despina, Wymeersch, Filip J., Huang, Yali, Kleinjung, Jens, Wilson, Valerie, Briscoe, James
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.05.2017; Cell Press
• Subjects: Animals; Body Patterning - physiology; Cell Differentiation - physiology; Cell Lineage - physiology; dynamical systems modeling; Gene Expression Regulation, Developmental - physiology; gene regulatory networks; Gene Regulatory Networks - physiology; Mesoderm - metabolism; neuromesodermal progenitors; NMPs; retinoic acid; single-cell transcriptome analysis; Spinal Cord - cytology; vertebrate development; Vertebrates - embryology; Wnt Signaling Pathway - physiology; single-cell transcriptome analysis; retinoic acid; gene regulatory networks; neuromesodermal progenitors; NMPs; vertebrate development; dynamical systems modeling
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2017.04.002

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. [Display omitted] •Single-cell RNA-seq reveals a signature of neuromesodermal progenitors•In vitro NMPs resemble and differentiate similar to their in vivo counterparts•Dual role for retinoic acid signaling in NMP induction and neural differentiation•A transcriptional network regulates neural versus mesodermal allocation Neuromesodermal progenitors (NMPs) generate cells of the spinal cord and somites. Gouti et al. demonstrate that in vitro NMPs resemble in vivo counterparts at the single-cell level and define a regulatory network that balances the generation of neural and mesodermal tissue to facilitate orderly extension of the embryonic axis.