Proliferation of Murine Midbrain Neural Stem Cells Depends upon an Endogenous Sonic Hedgehog (Shh) Source

Autor: Verónica Palma, Brandon J. Wainwright, Tammy Ellis, Natalia P. Solis, Víctor Hugo Cornejo, Constanza Martínez, Pablo Lois
Rok vydání: 2013
Předmět:
Cellular differentiation
Fluorescent Antibody Technique
lcsh:Medicine
Fibroblast growth factor
Mice
chemistry.chemical_compound
Neural Stem Cells
Mesencephalon
Pregnancy
Molecular Cell Biology
Stem Cell Niche
Sonic hedgehog
lcsh:Science
Cells
Cultured
In Situ Hybridization
Multidisciplinary
biology
Stem Cells
Cell Differentiation
Immunohistochemistry
Hedgehog signaling pathway
Neural stem cell
Cell biology
Patched-1 Receptor
embryonic structures
Female
Cellular Types
Research Article
Signal Transduction
Patched Receptors
Patched
animal structures
Cyclopamine
Neurogenesis
Blotting
Western
Receptors
Cell Surface
Developmental Neuroscience
Neurosphere
Animals
Hedgehog Proteins
Biology
Cell Proliferation
Epidermal Growth Factor
lcsh:R
Correction
Molecular Development
Signaling
Fibroblast Growth Factors
Mice
Inbred C57BL
chemistry
Immunology
biology.protein
lcsh:Q
Developmental Biology
Neuroscience
Zdroj: PLoS ONE, Vol 8, Iss 6, p e65818 (2013)
PLOS ONE
Artículos CONICYT
CONICYT Chile
instacron:CONICYT
PLoS ONE
ISSN: 1932-6203
Popis: The Sonic Hedgehog (Shh) pathway is responsible for critical patterning events early in development and for regulating the delicate balance between proliferation and differentiation in the developing and adult vertebrate brain. Currently, our knowledge of the potential role of Shh in regulating neural stem cells (NSC) is largely derived from analyses of the mammalian forebrain, but for dorsal midbrain development it is mostly unknown. For a detailed understanding of the role of Shh pathway for midbrain development in vivo, we took advantage of mouse embryos with cell autonomously activated Hedgehog (Hh) signaling in a conditional Patched 1 (Ptc1) mutant mouse model. This animal model shows an extensive embryonic tectal hypertrophy as a result of Hh pathway activation. In order to reveal the cellular and molecular origin of this in vivo phenotype, we established a novel culture system to evaluate neurospheres (nsps) viability, proliferation and differentiation. By recreating the three-dimensional (3-D) microenvironment we highlight the pivotal role of endogenous Shh in maintaining the stem cell potential of tectal radial glial cells (RGC) and progenitors by modulating their Ptc1 expression. We demonstrate that during late embryogenesis Shh enhances proliferation of NSC, whereas blockage of endogenous Shh signaling using cyclopamine, a potent Hh pathway inhibitor, produces the opposite effect. We propose that canonical Shh signaling plays a central role in the control of NSC behavior in the developing dorsal midbrain by acting as a niche factor by partially mediating the response of NSC to epidermal growth factor (EGF) and fibroblast growth factor (FGF) signaling. We conclude that endogenous Shh signaling is a critical mechanism regulating the proliferation of stem cell lineages in the embryonic dorsal tissue.
Databáze: OpenAIRE
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