An emerging molecular mechanism for the neural vs mesodermal cell fate decision

Li, Roman A.; Storey, Kate G.

doi:10.1038/cr.2011.54

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…Embryos lacking either Msgn1 or Tbx6 have defects in axis elongation, partial loss of mesodermal tissue, and enlarged tailbuds ( Chapman et al., 2003 , Chapman and Papaioannou, 1998 , Yoon and Wold, 2000 ). Tbx6 is important for the repression of Sox2 during mesoderm specification ( Li and Storey, 2011 , Takemoto et al., 2011 ). Conversely, overexpression of Msgn1 results in decreased neural induction ( Chalamalasetty et al., 2014 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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SummaryTranscriptional 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…The role of Wnt signaling in mesoderm and neural specification has been controversial (Li and Storey, 2011). Early studies in frogs have suggested that canonical Wnt signaling functions during gastrulation to induce neural tissue (Baker et al, 1999), whereas others have suggested that the gastrula stage role of Wnt signaling is to induce mesoderm (Schohl and Fagotto, 2003).…”

Section: Discussionmentioning

confidence: 99%

Canonical Wnt Signaling Dynamically Controls Multiple Stem Cell Fate Decisions during Vertebrate Body Formation

2012

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SUMMARY The vertebrate body forms in an anterior-to-posterior progression, driven by a population of undifferentiated cells at the posterior-most end of the embryo. Recent studies have demonstrated that these undifferentiated cells are multipotent stem cells, suggesting that local signaling factors specify cell fate. However, the mechanism of cell fate specification during this process is unknown. Using a combination of single cell transplantation and newly developed cell-autonomous inducible Wnt inhibitor and activator transgenic zebrafish lines, we show that canonical Wnt signaling is continuously necessary and sufficient to specify mesoderm from a bipotential neural/mesodermal precursor. Surprisingly, we also find that Wnt signaling functions subsequently within the mesoderm to specify somites instead of posterior vascular endothelium. Our results demonstrate that dynamic local Wnt signaling cues specify germ layer contribution and mesodermal tissue type specification of multipotent stem cells throughout the formation of the early vertebrate embryonic body.

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“…The co-expression of Sox2 and Bra is a central feature of NMps and there is some evidence that they are mutually repressive (indicated by dotted inhibition symbols). For example, Sox2 mRNA expression is high in Bra mutant NMps in which Wnt is activated (Gouti et al, 2014); in the frog, T-box genes directly repress Sox2 (Gentsch et al, 2013); and in the mouse the presomitic mesoderm gene Tbx6 represses Sox2 via the N1 enhancer (Li and Storey, 2011; Takemoto et al, 2011). Conversely, Sox2 N1 loss (in a Sox3 null background) increases the ingression of cells to form presomitic mesoderm (Yoshida et al, 2014), suggesting that Sox2 normally restrains this Bra-induced activity; Sox2 also binds the Bra promoter in ESC-derived neural progenitors and Sox2 overexpression represses Bra in a Wnt-driven mesodermal differentiation assay (Zhao et al, 2004; Thomson et al, 2011).…”

Section: Potential Applications Of Nmpsmentioning

confidence: 99%

Neuromesodermal progenitors and the making of the spinal cord

et al. 2015

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Neuromesodermal progenitors (NMps) contribute to both the elongating spinal cord and the adjacent paraxial mesoderm. It has been assumed that these cells arise as a result of patterning of the anterior neural plate. However, as the molecular mechanisms that specify NMps in vivo are uncovered, and as protocols for generating these bipotent cells from mouse and human pluripotent stem cells in vitro are established, the emerging data suggest that this view needs to be revised. Here, we review the characteristics, regulation, in vitro derivation and in vivo induction of NMps. We propose that these cells arise within primitive streak-associated epiblast via a mechanism that is separable from that which establishes neural fate in the anterior epiblast. We thus argue for the existence of two distinct routes for making central nervous system progenitors.

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An emerging molecular mechanism for the neural vs mesodermal cell fate decision

Cited by 7 publications

References 11 publications

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

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

Canonical Wnt Signaling Dynamically Controls Multiple Stem Cell Fate Decisions during Vertebrate Body Formation

Neuromesodermal progenitors and the making of the spinal cord

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