FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step epithelial to mesenchymal transition

Goto, Hana; Kimmey, Samuel C.; Row, Richard H.; Matus, David Q.; Martin, Benjamin L.

doi:10.1242/dev.143578

Cited by 79 publications

(97 citation statements)

References 80 publications

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“…A study in differentiating human ES cells also showed that FGF can efficiently induce expression of spinal cord markers in the absence of Wnt signaling [64]. Interestingly, at later stages of tailbud formation in the most posterior embryo regions, FGF and BMP were shown to be necessary for spinal cord formation in both zebrafish [31,65] and Xenopus embryos [66,67]. Canonical Wnt signaling was important for promoting mesoderm progenitor cells, but not neural progenitors in the posterior spinal cord [31].…”

Section: Discussionmentioning

confidence: 99%

New roles for Wnt and BMP signaling in neural anteroposterior patterning

et al. 2019

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During amphibian development, neural patterning occurs via a two‐step process. Spemann's organizer secretes BMP antagonists that induce anterior neural tissue. A subsequent caudalizing step re‐specifies anterior fated cells to posterior fates such as hindbrain and spinal cord. The neural patterning paradigm suggests that a canonical Wnt‐signaling gradient acts along the anteroposterior axis to pattern the nervous system. Wnt activity is highest in the posterior, inducing spinal cord, at intermediate levels in the trunk, inducing hindbrain, and is lowest in anterior fated forebrain, while BMP‐antagonist levels are constant along the axis. Our results in Xenopus laevis challenge this paradigm. We find that inhibition of canonical Wnt signaling or its downstream transcription factors eliminates hindbrain, but not spinal cord fates, an observation not compatible with a simple high‐to‐low Wnt gradient specifying all fates along the neural anteroposterior axis. Additionally, we find that BMP activity promotes posterior spinal cord cell fate formation in an FGF‐dependent manner, while inhibiting hindbrain fates. These results suggest a need to re‐evaluate the paradigms of neural anteroposterior pattern formation during vertebrate development.

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Section: Discussionmentioning

confidence: 99%

New roles for Wnt and BMP signaling in neural anteroposterior patterning

et al. 2019

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“…Indeed, co-expression of master regulators of mesoderm (T) and neural (Sox2) development fits well with the proposed potency of the dual-fated progenitors. Based on this assumption, T/Sox2 double-positive cells have been studied extensively in vitro [12][13][14][15] and in vivo 6,9,11,[16][17][18][19][20] . Despite the increasing interest in NMPs, their precise role in embryonic development still remains to be elucidated, though it is hypothesized that they are essential for body axis elongation 2,9,12,16,[20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

Genetic approaches in mice demonstrate that neuro-mesodermal progenitors express T/Brachyury but not Sox2

Mugele

Moulding

Savery

et al. 2018

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Neural tube and somites have long been thought to derive from separate germ layers: the ectoderm and mesoderm. This concept was challenged by the discovery of neuromesodermal progenitors, a bi-potent cell population that gives rise to both spinal neural tube and somites. In line with their proposed potency, these cells are considered to co-express the neural marker Sox2 and the mesodermal marker T/Brachyury. We performed genetic lineage tracing in mouse embryos and confirmed that T-expressing cells give rise to both neural tube and mesoderm. Surprisingly, however, Sox2-expressing cell derivatives colonise only the neural tube after embryonic day 8.5. Deletion of Sox2 in T-expressing cells was compatible with an otherwise normal neural tube and paraxial mesoderm. Moreover, Sox2 expression is absent from the chordoneural hinge, where neuro-mesodermal progenitors are located. Our findings demonstrate that neuro-mesodermal progenitors express T but notSox2, suggesting the need for re-evaluation of the neuro-mesodermal progenitor hypothesis.The initial aim of this study was to define the role of NMPs in neural tube formation, since it is not clear to what extent the progenitors contribute to this tissue. We traced cells either from the NSB or CLE into the closing neural tube, and found that the caudal end of the embryo harbours two distinct populations, both of which fulfil the criteria of NMPs, yet give rise to different domains within the closed neural tube. NMP function was addressed using laser ablation and a genetic approach, based on the proposed co-expression of T and Sox2.

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“…The EMT creates a pool of disorganized mesodermal progenitors in the medial tailbud that then segregate in a bilaterally symmetric manner into the paraxial mesoderm. In zebrafish, Wnt signaling regulates the first step in this EMT (Goto et al, 2017). Thus, over-expression of the Wnt inhibitor notum1a likely increases ordered cell motion by abrogating this EMT.…”

Section: Discussionmentioning

confidence: 99%

“…Trunk elongation involves the collective movement and proliferation of cells within the posterior edge of the embryo in a structure called the tailbud (Kanki and Ho, 1997; Lawton et al, 2013; McMillen and Holley, 2015; Quesada-Hernandez et al, 2010; Steventon et al, 2016; Wilson et al, 2009; Zhang et al, 2008) (Figure 1A, highlighted region). Throughout trunk elongation in the mouse, zebrafish and chick, a subset of prospective mesodermal cells undergo epithelial-to-mesenchymal transition (EMT) joining a pool of disordered mesenchymal progenitors that sort symmetrically into the paraxial mesoderm, which later develops into the skeletal muscle and vertebral column (Goto et al, 2017; Manning and Kimelman, 2015; Ohta et al, 2007; Wilson and Beddington, 1996). In zebrafish, this is a two-step EMT, with the first step regulated by Wnt signaling, and the second step regulated by Fgf signaling (Goto et al, 2017; Manning and Kimelman, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Throughout trunk elongation in the mouse, zebrafish and chick, a subset of prospective mesodermal cells undergo epithelial-to-mesenchymal transition (EMT) joining a pool of disordered mesenchymal progenitors that sort symmetrically into the paraxial mesoderm, which later develops into the skeletal muscle and vertebral column (Goto et al, 2017; Manning and Kimelman, 2015; Ohta et al, 2007; Wilson and Beddington, 1996). In zebrafish, this is a two-step EMT, with the first step regulated by Wnt signaling, and the second step regulated by Fgf signaling (Goto et al, 2017; Manning and Kimelman, 2015). …”

Section: Introductionmentioning

confidence: 99%

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Patterned Disordered Cell Motion Ensures Vertebral Column Symmetry

et al. 2017

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Summary The biomechanics of posterior embryonic growth must be dynamically regulated to ensure bilateral symmetry of the spinal column. Throughout vertebrate trunk elongation, motile mesodermal progenitors undergo an order to disorder transition via EMT and sort symmetrically into the left and right paraxial mesoderm. We combine theoretical modeling of cell migration in a tailbud-like geometry with experimental data analysis to assess the importance of ordered and disordered cell motion. We find that increasing order in cell motion causes a phase transition from symmetric to asymmetric body elongation. In silico and in vivo, overly ordered cell motion converts normal anisotropic fluxes into stable vortices near the posterior tailbud, contributing to asymmetric cell sorting. Thus, disorder is a physical mechanism that ensures the bilateral symmetry of the spinal column. These physical properties of the tissue connect across scales such that patterned disorder at the cellular level leads to the emergence of organism-level order.

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FGF and canonical Wnt signaling cooperate to induce paraxial mesoderm from tailbud neuromesodermal progenitors through regulation of a two-step epithelial to mesenchymal transition

Cited by 79 publications

References 80 publications

New roles for Wnt and BMP signaling in neural anteroposterior patterning

New roles for Wnt and BMP signaling in neural anteroposterior patterning

Genetic approaches in mice demonstrate that neuro-mesodermal progenitors express T/Brachyury but not Sox2

Patterned Disordered Cell Motion Ensures Vertebral Column Symmetry

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