Deconstructing the molecular mechanisms shaping the vertebrate body plan

Aires, Rita; Dias, André; Mallo, Moisés

doi:10.1016/j.ceb.2018.05.009

Cited by 27 publications

(34 citation statements)

References 49 publications

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“…NMPs express low levels of T and SOX2 and are detected in the nodestreak boarder and the caudal lateral epiblast during body elongation (Garriock et al, 2015;Wymeersch et al, 2016). NMPs are later relocated in the chordoneural hinge of the tail bud, where the posterior neural plate overlies the caudal notochord, and continue to contribute to the elongating tail (Aires et al, 2018). In addition, the expression of Nkx1.2 also marks NMPs and other progenitors (Rodrigo Albors et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos

et al. 2019

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Bi-potential neuromesodermal progenitors (NMPs) produce both neural and paraxial mesodermal progenitors in the trunk and tail during vertebrate body elongation. We show that Sall4, a pluripotency-related transcription factor gene, has multiple roles in regulating NMPs and their descendants in post-gastrulation mouse embryos. Sall4 deletion using TCre caused body/tail truncation, reminiscent of early depletion of NMPs, suggesting a role of Sall4 in NMP maintenance. This phenotype became significant at the time of the trunk-to-tail transition, suggesting that Sall4 maintenance of NMPs enables tail formation. Sall4 mutants exhibit expanded neural and reduced mesodermal tissues, indicating a role of Sall4 in NMP differentiation balance. Mechanistically, we show that Sall4 promotion of WNT/β-catenin signaling contributes to NMP maintenance and differentiation balance. RNA-Seq and SALL4 ChIP-Seq analyses support the notion that Sall4 regulates both mesodermal and neural development. Furthermore, in the mesodermal compartment, genes regulating presomitic mesoderm differentiation are downregulated in Sall4 mutants. In the neural compartment, we show that differentiation of NMPs towards post-mitotic neuron is accelerated in Sall4 mutants. Our results collectively provide evidence supporting the role of Sall4 in regulating NMPs and their descendants.

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Section: Introductionmentioning

confidence: 99%

Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos

et al. 2019

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“…In addition, paraxial mesoderm formation depends on a bi-potential population of neuro-mesodermal progenitor cells (NMP). In response to high levels of Wnt3a and CDX family members, these progenitors commit to mesoderm fates and give rise to neck, trunk and tail structures (Aires et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…For example, members of the HOXB cluster are first activated in a temporal colinear fashion in prospective paraxial mesoderm, prior to ingression through the primitive streak (Iimura and Pourquie, 2006). The colinear activation of HOX genes culminates in nested expression domains within the paraxial mesoderm, thereby conferring regional identity along the axis (Aires et al, 2018;Iimura et al, 2009). To determine the structural features associated with colinear expression the 3D organization of HOX clusters has been investigated (Noordermeer et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension

Mok

Folkes

Weldon

et al. 2020

Preprint

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The development of multicellular organisms is exquisitely regulated through differential gene activity, which governs cell differentiation programs. However, many details of spatiotemporal control of gene regulation are still poorly understood. We used the accessibility of chick embryos to examine genome-wide signatures characterizing the progressive differentiation of paraxial mesoderm along the head-to-tail axis. Paraxial mesoderm becomes organized into repetitive units, termed somites, the hallmark of the segmented vertebrate body plan. New somite pairs form periodically as the axis extends at the posterior end. This process generates a developmental gradient within a single embryo, with anterior somites more advanced in their differentiation compared to posterior somites. Following somite formation, cell rearrangements generate compartments, comprising lineages of the musculoskeletal system, including cartilage of the vertebral column and ribs, and skeletal muscle cells of the trunk and limbs. To examine how paraxial mesoderm becomes regionalized and patterned to eventually generate these discrete lineages, we investigated dynamic changes of the transcriptome and of chromatin accessibility using RNA-seq and ATAC-seq across a spatiotemporal series along the embryonic axis. Footprint analysis uncovers differential coverage of binding sites for a number of key transcription factors known to be involved in axial patterning and differentiation, including HOX genes. Furthermore, associating accessible chromatin with nearby expressed genes identifies candidate cis-regulatory elements (CRE). As exemplars we use TCF15 and MEOX1, which are crucial for somite formation and differentiation, to experimentally validate CREs in vivo using fluorescent reporters. Time-lapse microscopy reveals CRE spatiotemporal activity and mutation analysis uncovers necessary upstream regulators. The CRE for MEOX1 is conserved and recognized in Xenopus. In addition, a human element is active in chicken.In vivo epigenome editing of TCF15 and MEOX1 CREs disrupts gene expression regulation and recapitulates phenotypic abnormalities of anterior-posterior axis extension.3

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“…At the end of gastrulation, during the so-called primary body 5 formation (i.e. post-occipital region of the head, neck and trunk) axial progenitors are 6 located in the epiblast, an epithelial layer at the caudal embryonic end, and their 7 activity is organized by the primitive streak (PS) (Aires et al, 2018;Holmdahl, 1925;8 Steventon and Martinez Arias, 2017). At this stage the embryo contains axial 9 progenitors with different potential.…”

Section: Introductionmentioning

confidence: 99%

A TgfβRI/Snai1-dependent developmental module at the core of vertebrate axial elongation

Dias

Lozovska

Wymeersch

et al. 2020

Preprint

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Formation of the vertebrate postcranial body axis follows two sequential but distinct phases. The first phase generates pre-sacral structures (the so-called primary body) through the activity of the primitive streak (PS) on axial progenitors within the epiblast. The embryo then switches to generate the secondary body (post-sacral structures), which depends on axial progenitors in the tail bud. Here we show that the mammalian tail bud is generated through an independent developmental module, concurrent but functionally different to that generating the primary body. This module is triggered by convergent TgfβRI and Snai1 activities that promote an incomplete epithelial to mesenchymal transition (EMT) on a subset of epiblast axial progenitors. This EMT is functionally different to that coordinated by the PS, as it does not lead to mesodermal differentiation but brings axial progenitors into a transitory state, keeping their progenitor activity to drive further axial body extension.

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Deconstructing the molecular mechanisms shaping the vertebrate body plan

Cited by 27 publications

References 49 publications

Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos

Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos

Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension

A TgfβRI/Snai1-dependent developmental module at the core of vertebrate axial elongation

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