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Journal of Neuroscience
Article . 2011 . Peer-reviewed
License: CC BY NC SA
Data sources: Crossref
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Subregional Specification of Embryonic Stem Cell-Derived Ventral Telencephalic Tissues by Timed and Combinatory Treatment with Extrinsic Signals

Authors: Masako Kawada; Yuchio Yanagawa; Keiko Muguruma; Teruko Danjo; Yoshiki Sasai; Kiichi Watanabe; Mototsugu Eiraku; +1 Authors

Subregional Specification of Embryonic Stem Cell-Derived Ventral Telencephalic Tissues by Timed and Combinatory Treatment with Extrinsic Signals

Abstract

During early telencephalic development, the major portion of the ventral telencephalic (subpallial) region becomes subdivided into three regions, the lateral (LGE), medial (MGE), and caudal (CGE) ganglionic eminences. In this study, we systematically recapitulated subpallial patterning in mouse embryonic stem cell (ESC) cultures and investigated temporal and combinatory actions of patterning signals. In serum-free floating culture, the dorsal-ventral specification of ESC-derived telencephalic neuroectoderm is dose-dependently directed by Sonic hedgehog (Shh) signaling. Early Shh treatment, even before the expression onset of Foxg1 (also Bf1; earliest marker of the telencephalic lineage), is critical for efficiently generating LGE progenitors, and continuous Shh signaling until day 9 is necessary to commit these cells to the LGE lineage. When induced under these conditions and purified by fluorescence-activated cell sorter, telencephalic cells efficiently differentiated into Nolz1+/Ctip2+LGE neuronal precursors and subsequently, both in culture and afterin vivografting, into DARPP32+medium-sized spiny neurons. Purified telencephalic progenitors treated with high doses of the Hedgehog (Hh) agonist SAG (Smoothened agonist) differentiated into MGE- and CGE-like tissues. Interestingly, in addition to strong Hh signaling, the efficient specification of MGE cells requires Fgf8 signaling but is inhibited by treatment with Fgf15/19. In contrast, CGE differentiation is promoted by Fgf15/19 but suppressed by Fgf8, suggesting that specific Fgf signals play different, critical roles in the positional specification of ESC-derived ventral subpallial tissues. We discuss a model of the antagonistic Fgf8 and Fgf15/19 signaling in rostral-caudal subpallial patterning and compare it with the roles of these molecules in cortical patterning.

Keywords

Neurons, Cyclohexylamines, Fibroblast Growth Factor 8, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Cell Differentiation, Forkhead Transcription Factors, Nerve Tissue Proteins, Flow Cytometry, Immunohistochemistry, Polymerase Chain Reaction, Fibroblast Growth Factors, Repressor Proteins, Mice, Animals, Hedgehog Proteins, Carrier Proteins, Cells, Cultured, Embryonic Stem Cells, Signal Transduction

  • BIP!
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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    158
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
158
Top 1%
Top 10%
Top 1%
hybrid