scholarly journals Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ayse Güven ◽  
Nereo Kalebic ◽  
Katherine R Long ◽  
Marta Florio ◽  
Samir Vaid ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Integrin Signaling ◽  
Proliferative Capacity ◽  
Sox9 Expression ◽  
Embryonic Mouse ◽  
Basal Progenitor ◽  
Layer Neuron ◽  
Developing Neocortex ◽  
Stimulation Of

Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that the transcription factor Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. We show that Sox9 is expressed in human and ferret BPs and is required for BP proliferation in embryonic ferret neocortex. Conditional Sox9 expression in the mouse BP lineage, where it normally is not expressed, increases BP proliferation, reduces Tbr2 levels and induces Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell-non-autonomous stimulation of BP proliferation followed by increased upper-layer neuron production. Our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic vs. gliogenic BP cell fate, suggesting that Sox9 may have contributed to promote neocortical expansion.

scholarly journals Extracellular matrix-inducing Sox9 orchestrates basal progenitor proliferation and gliogenesis in developing neocortex

2019 ◽  
Author(s):  
Ayse Güven ◽  
Denise Stenzel ◽  
Katherine R. Long ◽  
Marta Florio ◽  
Holger Brandl ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Subventricular Zone ◽  
Integrin Signaling ◽  
Sox9 Expression ◽  
Embryonic Mouse ◽  
Functional Studies ◽  
Basal Progenitor ◽  
Developing Neocortex ◽  
Stimulation Of

AbstractNeocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. Examination of Sox9 expression reveals that Sox9 is expressed in BPs of developing ferret and human, but not mouse neocortex. Functional studies by conditional Sox9 expression in the mouse BP lineage demonstrate increased BP proliferation, reduced Tbr2 and induction of Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell non-autonomous stimulation of BP proliferation followed by increased production of upper-layer neurons. Collectively, our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic as well as gliogenic BP cell fate, suggesting that Sox9 acts a master regulator in the subventricular zone to promote neocortical expansion.

Use of Flexible Materials with a Novel Pressure Driven Equibiaxial Cell Stretching Device for Mechanical Stimulation of Single Mammalian Cells

2003 ◽  
Vol 773 ◽  
Author(s):  
James D. Kubicek ◽  
Stephanie Brelsford ◽  
Philip R. LeDuc
Keyword(s):  
Cell Fate ◽  
Mechanical Stimulation ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Single Cells ◽  
Complex Nature ◽  
Cellular Behavior ◽  
Cell Stretching ◽  
Stimulation Of ◽  
Pressure Driven

AbstractMechanical stimulation of single cells has been shown to affect cellular behavior from the molecular scale to ultimate cell fate including apoptosis and proliferation. In this, the ability to control the spatiotemporal application of force on cells through their extracellular matrix connections is critical to understand the cellular response of mechanotransduction. Here, we develop and utilize a novel pressure-driven equibiaxial cell stretching device (PECS) combined with an elastomeric material to control specifically the mechanical stimulation on single cells. Cells were cultured on silicone membranes coated with molecular matrices and then a uniform pressure was introduced to the opposite surface of the membrane to stretch single cells equibiaxially. This allowed us to apply mechanical deformation to investigate the complex nature of cell shape and structure. These results will enhance our knowledge of cellular and molecular function as well as provide insights into fields including biomechanics, tissue engineering, and drug discovery.

scholarly journals Modulating Tumor Cell Functions by Tunable Nanopatterned Ligand Presentation

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Katharina Amschler ◽  
Michael P. Schön
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Cell Fate ◽  
Epithelial Mesenchymal Transition ◽  
Model Systems ◽  
Cellular Functions ◽  
Biophysical Parameters ◽  
Ligand Density ◽  
Mesenchymal Transition ◽  
Cell Functions

Cancer comprises a large group of complex diseases which arise from the misrouted interplay of mutated cells with other cells and the extracellular matrix. The extracellular matrix is a highly dynamic structure providing biochemical and biophysical cues that regulate tumor cell behavior. While the relevance of biochemical signals has been appreciated, the complex input of biophysical properties like the variation of ligand density and distribution is a relatively new field in cancer research. Nanotechnology has become a very promising tool to mimic the physiological dimension of biophysical signals and their positive (i.e., growth-promoting) and negative (i.e., anti-tumoral or cytotoxic) effects on cellular functions. Here, we review tumor-associated cellular functions such as proliferation, epithelial-mesenchymal transition (EMT), invasion, and phenotype switch that are regulated by biophysical parameters such as ligand density or substrate elasticity. We also address the question of how such factors exert inhibitory or even toxic effects upon tumor cells. We describe three principles of nanostructured model systems based on block copolymer nanolithography, electron beam lithography, and DNA origami that have contributed to our understanding of how biophysical signals direct cancer cell fate.

Cellular modulation by the elasticity of biomaterials

2016 ◽  
Vol 4 (1) ◽  
pp. 9-26 ◽  
Author(s):  
Fengxuan Han ◽  
Caihong Zhu ◽  
Qianping Guo ◽  
Huilin Yang ◽  
Bin Li
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Matrix Elasticity ◽  
Recent Advances

The elasticity of the extracellular matrix has been increasingly recognized as a dominating factor of cell fate and activities. This review provides an overview of the general principles and recent advances in the field of matrix elasticity-dependent regulation of a variety of cellular activities and functions, the underlying biomechanical and molecular mechanisms, as well as the pathophysiological implications.

scholarly journals Breast tumour initiating cell fate is regulated by microenvironmental cues from an extracellular matrix

2012 ◽  
Vol 4 (8) ◽  
pp. 897 ◽  
Author(s):  
Sharmistha Saha ◽  
Pang-Kuo Lo ◽  
Xinrui Duan ◽  
Hexin Chen ◽  
Qian Wang
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Breast Tumour

scholarly journals Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate

2014 ◽  
Vol 2 (3) ◽  
pp. 381-389 ◽  
Author(s):  
J. Ballester-Beltrán ◽  
D. Moratal ◽  
M. Lebourg ◽  
M. Salmerón-Sánchez
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Natural Environment ◽  
Fibronectin Matrix

Conventional 2D substrates fail to represent the natural environment of cells surrounded by the 3D extracellular matrix (ECM).

scholarly journals Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: effects of beta-D-xyloside, an inhibitor of branching morphogenesis.

1983 ◽  
Vol 96 (5) ◽  
pp. 1443-1450 ◽  
Author(s):  
H A Thompson ◽  
B S Spooner
Keyword(s):  
Salivary Glands ◽  
Dermatan Sulfate ◽  
Branching Morphogenesis ◽  
Proteoglycan Synthesis ◽  
Embryonic Mouse ◽  
Glycosaminoglycan Synthesis ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulation Of

The proteoglycans and glycosaminoglycans synthesized by embryonic mouse salivary glands during normal morphogenesis and in the presence of beta-xyloside, an inhibitor of branching morphogenesis, have been partially characterized. Control and rho-nitrophenyl-beta-D-xyloside-treated salivary rudiments synthesize proteoglycans that are qualitatively similar, based on mobility on Sepharose CL-4B under dissociative conditions and glycosaminoglycan composition. However, beta-xyloside inhibits total proteoglycan-associated glycosaminoglycan synthesis by 50%, and also stimulates synthesis of large amounts of free chondroitin (dermatan) sulfate. This free glycosaminoglycan accounts for the threefold stimulation of total glycosaminoglycan synthesis in beta-xyloside-treated cultures. Several observations suggest that the disruption of proteoglycan synthesis rather than the presence of large amounts of free glycosaminoglycan is responsible for the inhibition of branching morphogenesis. (a) We have been unable to inhibit branching activity by adding large amounts of chondroitin (dermatan) sulfate, extracted from beta-xyloside-treated cultures, to the medium of salivary rudiments undergoing morphogenesis. (b) In the range of 0.1-0.4 mM beta-xyloside, the dose-dependent inhibition of branching morphogenesis is directly correlated with the inhibition of proteoglycan synthesis. The stimulation of free glycosaminoglycan synthesis is independent of dose in this range, since stimulation is maximal even at the lowest concentration used, 0.1 mM. The data strongly suggest that the inhibition of branching morphogenesis is caused by the disruption of proteoglycan synthesis in beta-xyloside-treated salivary glands.

scholarly journals The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

2019 ◽  
Vol 106 ◽  
pp. 49-56 ◽  
Author(s):  
Natalia Sánchez-Romero ◽  
Pilar Sainz-Arnal ◽  
Iris Pla-Palacín ◽  
Pablo Royo Dachary ◽  
Helen Almeida ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Dynamic Relationship ◽  
Health And Disease
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