Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin

Long, Katherine R.; Moss, Lara; Laursen, Lisbeth S.; Boulter, Luke; ffrench‐Constant, Charles

doi:10.1038/ncomms10354

Cited by 57 publications

(48 citation statements)

References 59 publications

(84 reference statements)

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“…However, although we cannot exclude that other miRNAs/specific targets could have a role during this early developmental period, it is more likely that the absence of Dicer in highly proliferating cells is linked to replication-associated DNA damage as recently shown in the developing cerebellum. 31 Integrin signaling is also known to be involved in cell proliferation 53,54 and could thus be linked to the defective cell cycle arrest of Sox2 progenitors observed in Dicer-cKO animals. Consistently, ItgA3 overexpression induces ongoing proliferation of UB-OC1 cells cultured in non-proliferative conditions.…”

Section: Discussionmentioning

confidence: 99%

The miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development

et al. 2017

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MicroRNAs are important regulators of gene expression and are involved in cellular processes such as proliferation or differentiation, particularly during development of numerous organs including the inner ear. However, it remains unknown if miRNAs are required during the earliest stages of otocyst and cochlear duct development. Here, we report that a conditional loss of Dicer expression in the otocyst impairs the early development of the inner ear as a result of the accumulation of DNA damage that trigger p53-mediated apoptosis. Moreover, cochlear progenitors in the prosensory domain do not exit the cell cycle. Our unbiased approach identified ItgA3 as a target of miR-183, which are both enriched in the otic vesicle. We observed that the repression of integrin alpha 3 by miR-183 controls cell proliferation in the developing cochlea. Collectively, our results reveal that Dicer and miRNAs play essential roles in the regulation of early inner ear development.

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Section: Discussionmentioning

confidence: 99%

The miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development

et al. 2017

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“…Actomyosin-driven contraction of cells leads to stiffening of dorsal tissues, which is required for vertebrate neural tube closure (Zhou et al, 2009), and dysregulation of cell adhesion in neural folds, cell migration from the neural crest, or other mechanically regulated processes can result in severe neural tube defects (Greene and Copp, 2009). In the embryonic mesencephalon, β1 integrin activity enhances neurogenesis through a Wnt7a-dependent mechanism (Long et al, 2016). These studies indicate that abundant cellular movements and organizational changes occur during embryogenesis and as the primitive nervous system forms.…”

Section: Mechanical Forces Guide Brain Developmentmentioning

confidence: 93%

Tissue mechanics regulate brain development, homeostasis and disease

Barnes

Przybyla

Weaver

2017

Journal of Cell Science

262

245

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All cells sense and integrate mechanical and biochemical cues from their environment to orchestrate organismal development and maintain tissue homeostasis. Mechanotransduction is the evolutionarily conserved process whereby mechanical force is translated into biochemical signals that can influence cell differentiation, survival, proliferation and migration to change tissue behavior. Not surprisingly, disease develops if these mechanical cues are abnormal or are misinterpreted by the cells – for example, when interstitial pressure or compression force aberrantly increases, or the extracellular matrix (ECM) abnormally stiffens. Disease might also develop if the ability of cells to regulate their contractility becomes corrupted. Consistently, disease states, such as cardiovascular disease, fibrosis and cancer, are characterized by dramatic changes in cell and tissue mechanics, and dysregulation of forces at the cell and tissue level can activate mechanosignaling to compromise tissue integrity and function, and promote disease progression. In this Commentary, we discuss the impact of cell and tissue mechanics on tissue homeostasis and disease, focusing on their role in brain development, homeostasis and neural degeneration, as well as in brain cancer.

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“…α6β1 integrin expression correlates with stem cell properties. Indeed, during cortical development, enhanced integrin β1 signaling in the chick neuroepithelium increases the expansion of Sox2+ cells and inhibits their differentiation (Long et al, 2016). In mice, β1-dependent anchoring of radial glia NSCs to laminin-rich ventricular surface regulates interkinetic nuclear migration and division orientation of NSC, two parameters necessary for proper cortical lamination (Belvindrah et al, 2007; Loulier et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and α6β1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties

Rosa

Grade

Santos

et al. 2016

Front. Cell. Neurosci.

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Neurogenesis in the subventricular zone (SVZ) is regulated by diffusible factors and cell–cell contacts. In vivo, SVZ stem cells are associated with the abluminal surface of blood vessels and such interactions are thought to regulate their neurogenic capacity. SVZ neural stem cells (NSCs) have been described to contact endothelial-derived laminin via α6β1 integrin. To elucidate whether heterocellular contacts with brain endothelial cells (BEC) regulate SVZ cells neurogenic capacities, cocultures of SVZ neurospheres and primary BEC, both obtained from C57BL/6 mice, were performed. The involvement of laminin-integrin interactions in SVZ homeostasis was tested in three ways. Firstly, SVZ cells were analyzed following incubation of BEC with the protein synthesis inhibitor cycloheximide (CHX) prior to coculture, a treatment expected to decrease membrane proteins. Secondly, SVZ cells were cocultured with BEC in the presence of an anti-α6 integrin neutralizing antibody. Thirdly, BEC were cultured with β1−/− SVZ cells. We showed that contact with BEC supports, at least in part, proliferation and stemness of SVZ cells, as evaluated by the number of BrdU positive (+) and Sox2+ cells in contact with BEC. These effects are dependent on BEC-derived laminin binding to α6β1 integrin and are decreased in cocultures incubated with anti-α6 integrin neutralizing antibody and in cocultures with SVZ β1−/− cells. Moreover, BEC-derived laminin sustains stemness in SVZ cell cultures via activation of the Notch and mTOR signaling pathways. Our results show that BEC/SVZ interactions involving α6β1 integrin binding to laminin, contribute to SVZ cell proliferation and stemness.

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Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin

Cited by 57 publications

References 59 publications

The miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development

The miR-183/ItgA3 axis is a key regulator of prosensory area during early inner ear development

Tissue mechanics regulate brain development, homeostasis and disease

Heterocellular Contacts with Mouse Brain Endothelial Cells Via Laminin and α6β1 Integrin Sustain Subventricular Zone (SVZ) Stem/Progenitor Cells Properties

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