Cell intercalation driven by SMAD3 underlies secondary neural tube formation

Gonzalez-Gobartt, Elena; Blanco-Ameijeiras, José; Usieto, Susana; Allio, Guillaume; Bénazéraf, Bertrand; Martı́, Elisa

doi:10.1016/j.devcel.2021.03.023

Cited by 19 publications

(24 citation statements)

References 87 publications

(72 reference statements)

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“…that present different local tissue mechanics (Zhou et al, 2009), which may also contribute to the morphogenesis of a single neural tube. Finally, recent reports in chick have described the fusion of multiple lumens into a single neural tube during secondary neurulation, when the most caudal region of the embryo is formed (Gonzalez-Gobartt et al, 2021). Thus, it is possible that human PSC-derived elongating organoids emulate early stages of a similar lumen fusion process to form a single neural tube.…”

Section: Discussionmentioning

confidence: 98%

Axial elongation of caudalized human organoids mimics aspects of neural tube development

et al. 2021

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Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model of neural tube extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Elongating organoids consist largely of neuroepithelial compartments and contain TBXT+SOX2+ neuro-mesodermal progenitors in addition to PAX6+NES+ neural progenitors. A critical threshold of Wnt agonism stimulated singular axial extensions while maintaining multiple cell lineages, such that organoids displayed regionalized anterior-to-posterior HOX gene expression with hindbrain (HOXB1) regions spatially distinct from brachial (HOXC6) and thoracic (HOXB9) regions. CRISPR interference-mediated silencing of TBXT, a Wnt pathway target, increased neuroepithelial compartmentalization, abrogated HOX expression and disrupted uniaxial elongation. Together, these results demonstrate the potent capacity of caudalized hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.

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Section: Discussionmentioning

confidence: 98%

Axial elongation of caudalized human organoids mimics aspects of neural tube development

et al. 2021

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“…4C). Recent studies show that SMAD3 drives cell intercalation underlies secondary neural tube formation in the mouse embryo (Gonzalez-Gobartt et al, 2021). Moreover, it was known that the BMP-Rho-ROCK1 pathway targets MLC to control actin remodeling in fibroblasts (Konstantinidis et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization

Kogure

Muraoka

Koizumi

et al. 2021

Preprint

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Chordate tailbud embryos have similar morphological features, including a bending tail. A recent study revealed that the actomyosin of the notochord changes the contractility and drive tail bending of the early Ciona tailbud embryo. Yet, the upstream regulator of tail bending remains unknown. In this study, we find that Admp regulates tail bending of Ciona mid-tailbud embryos. Anti-pSmad antibody signal was detected at the ventral midline tail epidermis. Admp knock-down embryo completely inhibited the ventral tail bending and reduced the number of the triangular-shaped cells, which has the apical accumulation of the myosin phosphorylation and inhibited specifically the cell-cell intercalation of the ventral epidermis. The degree of myosin phosphorylation of the ventral cells and tail bending were correlated. Finally, the laser cutter experiments demonstrated the myosin-phosphorylation-dependent tension of the ventral midline epidermis during tail bending. We conclude that Admp is an upstream regulator of the tail bending by controlling myosin phosphorylation and its localization of ventral epidermal cells. These data reveal a new aspect of the function of the Admp that might be evolutionarily conserved in bilaterian animals.

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“…Mesodermal cells undergo a mesenchymal to epithelial transition (MET) to form an epithelial tube that then fuses with the neural tube formed by primary NTC. When the mesodermal cells are prevented from undergoing epithelialization, the cells fail to participate in neural tube formation, and instead accumulate in the neural canal (Nakaya et al, 2004) Chick embryos in which SMAD3 is disrupted, a receptor involved in transforming growth factor β (TGF-β) signaling, display disrupted secondary neural tube formation marked by multiple small lumen (Gonzalez-Gobartt et al, 2021). SMAD3 seems unique among other SMAD proteins in directing cell migration during secondary neural tube formation (Gonzalez-Gobartt et al, 2021).…”

Section: Migrationmentioning

confidence: 99%

“…When the mesodermal cells are prevented from undergoing epithelialization, the cells fail to participate in neural tube formation, and instead accumulate in the neural canal (Nakaya et al, 2004) Chick embryos in which SMAD3 is disrupted, a receptor involved in transforming growth factor β (TGF-β) signaling, display disrupted secondary neural tube formation marked by multiple small lumen (Gonzalez-Gobartt et al, 2021). SMAD3 seems unique among other SMAD proteins in directing cell migration during secondary neural tube formation (Gonzalez-Gobartt et al, 2021). TGF-β signaling has been previously implicated in chick brain medial hinge point (MHP) formation (Nikolopoulou et al, 2017).…”

Section: Migrationmentioning

confidence: 99%

Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure

Engelhardt

Martyr

Niswander

2022

WIREs Mechanisms of Disease

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Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three‐dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide. Though NTDs are all defined as incomplete closure of the neural tube, the pathogenesis of an NTD determines the type, severity, positioning, and accompanying phenotypes. In this review, we survey pathogenesis of NTDs relating to disruption of cellular processes arising from genetic mutations, altered epigenetic regulation, and environmental influences by micronutrients and maternal condition. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development

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Cell intercalation driven by SMAD3 underlies secondary neural tube formation

Cited by 19 publications

References 87 publications

Axial elongation of caudalized human organoids mimics aspects of neural tube development

Axial elongation of caudalized human organoids mimics aspects of neural tube development

Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization

Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure

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