Development of a straight vertebrate body axis

Bagnat, Michel; Gray, Ryan S.

doi:10.1242/dev.175794

Cited by 52 publications

(44 citation statements)

References 141 publications

(219 reference statements)

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“…This ranges from ascidians, where notochord morphogenesis occurs in a population Development • Accepted manuscript of exactly 40 post-mitotic cells (Miyamoto and Crowther, 1985;Veeman and Smith, 2013), to amniotes that extensively elongate the notochord primordium after gastrulation through proliferation of posterior axial progenitors, and widespread intercalatory cell division (Cambray and Wilson, 2002;Catala et al, 1996;Selleck and Stern, 1991). Cell intercalation is generally followed by vacuolation of individual notochord cells, which expands their volume and increases notochord length and rigidity (Adams et al, 1990;Bagnat and Gray, 2020;Bancroft and Bellairs, 1976;Ellis et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Single-cell morphometrics reveals ancestral principles of notochord development

et al. 2021

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Embryonic tissues are shaped by the dynamic behaviours of their constituent cells. To understand such cell behaviours and how they evolved, new approaches are needed to map out morphogenesis across different organisms. Here, we apply a quantitative approach to learn how the notochord forms during the development of amphioxus, a basally-branching chordate. Using a single-cell morphometrics pipeline, we quantify the geometries of thousands of amphioxus notochord cells, and project them into a common mathematical space, termed morphospace. In morphospace, notochord cells disperse into branching trajectories of cell shape change, revealing a dynamic interplay between cell shape change and growth that collectively contribute to tissue elongation. By spatially mapping these trajectories, we identify conspicuous regional variation, both in developmental timing and trajectory topology. Finally, we show experimentally that, unlike ascidians but like vertebrates, posterior cell division is required in amphioxus to generate full notochord length, thereby suggesting this might be an ancestral chordate trait secondarily lost in ascidians. Altogether, our novel approach reveals that an unexpectedly complex scheme of notochord morphogenesis might have been present in the first chordates.

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Section: Introductionmentioning

confidence: 99%

Single-cell morphometrics reveals ancestral principles of notochord development

et al. 2021

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“…The spine is further supported by the paraspinal ligaments and provides attachment sites for multiple muscle-tendon insertions. Finally, the structural organization of the axial skeleton aids in the protection of the spinal cord and acts as the central axis of the body to support and maintain posture during movement through the environment ( Bagnat and Gray, 2020 ; Bogduk, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment

Liu

Hussien

Wang

et al. 2021

eLife

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Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs, and dense connective tissues (i.e., ligaments and tendons) are essential for the maintenance of spinal alignment. We show that the adhesion G protein-coupled receptor ADGRG6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine alignment in mice. Furthermore, we show that ADGRG6 regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with a cAMP agonist could mirror aspects of receptor function in culture, thus defining core pathways for regulating these axial cartilaginous and connective tissues. As ADGRG6 is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.

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“…The spine is further supported by the paraspinal ligaments and provides attachment sites for multiple muscle-tendon insertions. Finally, the structural organization of the axial spine aids in the protection of the spinal cord and acts as the central axis of the body to support and maintain posture during movement through the environment (Bagnat and Gray, 2020; Bogduk, 2016).…”

Section: Introductionmentioning

confidence: 99%

A G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment

Liu

Hussien

Wang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs and dense connective tissues (e.g., ligaments and tendons), are essential for maintenance of spinal alignment. We show that the G-coupled protein receptor Adgrg6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine morphology. We show that Adgrg6 regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with an cAMP agonist was able to mirror aspects of receptor function in culture defining core pathways for regulation of these axial connective tissues. As ADGRG6 is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.

show abstract

Development of a straight vertebrate body axis

Cited by 52 publications

References 141 publications

Single-cell morphometrics reveals ancestral principles of notochord development

Single-cell morphometrics reveals ancestral principles of notochord development

An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment

A G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment

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