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Coordination of progenitor specification and growth in mouse and chick spinal cord.

ABSTRACT: Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand.

SUBMITTER: Kicheva A

PROVIDER: S-EPMC4228193 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Coordination of progenitor specification and growth in mouse and chick spinal cord.

Kicheva Anna A Bollenbach Tobias T Ribeiro Ana A Valle Helena Pérez HP Lovell-Badge Robin R Episkopou Vasso V Briscoe James J

Science (New York, N.Y.) 20140901 6204

Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific r ...[more]

PMID: 25258086

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Project description:ObjectivesWe have evaluated the physiological roles of transforming growth factor-beta1 (TGF-beta1) on differentiation, migration, proliferation and anti-apoptosis characteristics of cultured spinal cord-derived neural progenitor cells.MethodsWe have used neural progenitor cells that had been isolated and cultured from mouse spinal cord tissue, and we also assessed the relevant reaction mechanisms using an activin-like kinase (ALK)-specific inhibitory system including an inhibitory RNA, and found that it involved potential signalling molecules such as phosphatidylinositol-3-OH kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2).Results and conclusionsTransforming growth factor-beta1-mediated cell population growth was activated after treatment and was also effectively blocked by an ALK41517-synthetic inhibitor (4-(5-benzo(1,3) dioxol-5-yl-4-pyridine-2-yl-1H-imidazole-2-yl) benzamide (SB431542) and ALK siRNA, thereby indicating the involvement of SMAD2 in the TGF-beta1-mediated growth and migration of these neural progenitors cells (NPC). In the present study, TGF-beta1 actively induced NPC migration in vitro. Furthermore, TGF-beta1 demonstrated extreme anti-apoptotic behaviour against hydrogen peroxide-mediated apoptotic cell death. At low dosages, TGF-beta1 enhanced (by approximately 76%) cell survival against hydrogen peroxide treatment via inactivation of caspase-3 and -9. TGF-beta1-treated NPCs down-regulated Bax expression and cytochrome c release; in addition, the cells showed up-regulated Bcl-2 and thioredoxin reductase 1. They also had increased p38, Akt and ERK1/2 phosphorylation, showing the involvement of both the PI3K/Akt and MAPK/ERK1/2 pathways in the neuroprotective effects of TGF-beta1. Interestingly, these effects operate on specific subtypes of cells, including neurones, neural progenitor cells and astrocytes in cultured spinal cord tissue-derived cells. Lesion sites of spinal cord-overexpressing TGF-beta1-mediated prevention of cell death, cell growth and migration enhancement activity have been introduced as a possible new basis for therapeutic strategy in treatment of neurodegenerative disorders, including spinal cord injuries.

Dataset Information

Coordination of progenitor specification and growth in mouse and chick spinal cord.

Publications

Coordination of progenitor specification and growth in mouse and chick spinal cord.

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