Subregional specification of embryonic stem cell-derived ventral telencephalic tissues by timed and combinatory treatment with extrinsic signals
- PMID: 21289201
- PMCID: PMC6623725
- DOI: 10.1523/JNEUROSCI.5128-10.2011
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 after in vivo grafting, 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.
Figures






Similar articles
-
The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice.Development. 2010 Feb;137(3):487-97. doi: 10.1242/dev.039800. Development. 2010. PMID: 20081193 Free PMC article.
-
Pharmacological modulation of the Hedgehog pathway differentially affects dorsal/ventral patterning in mouse and human embryonic stem cell models of telencephalic development.Stem Cells Dev. 2012 May 1;21(7):1016-46. doi: 10.1089/scd.2011.0271. Epub 2012 Feb 8. Stem Cells Dev. 2012. PMID: 22204396
-
FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development.Neural Dev. 2008 Jul 14;3:17. doi: 10.1186/1749-8104-3-17. Neural Dev. 2008. PMID: 18625063 Free PMC article.
-
Sonic hedgehog functions through dynamic changes in temporal competence in the developing forebrain.Curr Opin Genet Dev. 2010 Aug;20(4):391-9. doi: 10.1016/j.gde.2010.04.008. Epub 2010 May 11. Curr Opin Genet Dev. 2010. PMID: 20466536 Free PMC article. Review.
-
Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors.Birth Defects Res C Embryo Today. 2006 Sep;78(3):256-66. doi: 10.1002/bdrc.20077. Birth Defects Res C Embryo Today. 2006. PMID: 17061260 Review.
Cited by
-
Two-Phase Lineage Specification of Telencephalon Progenitors Generated From Mouse Embryonic Stem Cells.Front Cell Dev Biol. 2021 Apr 16;9:632381. doi: 10.3389/fcell.2021.632381. eCollection 2021. Front Cell Dev Biol. 2021. PMID: 33937233 Free PMC article.
-
Mouse embryonic stem cell culture for generation of three-dimensional retinal and cortical tissues.Nat Protoc. 2011 Dec 15;7(1):69-79. doi: 10.1038/nprot.2011.429. Nat Protoc. 2011. PMID: 22179593
-
Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease.Front Cell Neurosci. 2013 Mar 13;7:10. doi: 10.3389/fncel.2013.00010. eCollection 2013. Front Cell Neurosci. 2013. PMID: 23493959 Free PMC article.
-
Deriving excitatory neurons of the neocortex from pluripotent stem cells.Neuron. 2011 May 26;70(4):645-60. doi: 10.1016/j.neuron.2011.05.006. Neuron. 2011. PMID: 21609822 Free PMC article. Review.
-
Multiscale engineering of brain organoids for disease modeling.Adv Drug Deliv Rev. 2024 Jul;210:115344. doi: 10.1016/j.addr.2024.115344. Epub 2024 May 27. Adv Drug Deliv Rev. 2024. PMID: 38810702 Review.
References
-
- Agoston DV, Szemes M, Dobi A, Palkovits M, Georgopoulos K, Gyorgy A, Ring MA. Ikaros is expressed in developing striatal neurons and involved in enkephalinergic differentiation. J Neurochem. 2007;102:1805–1816. - PubMed
-
- Anderson SA, Eisenstat DD, Shi L, Rubenstein JL. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science. 1997;278:474–476. - PubMed
-
- Anderson SA, Marín O, Horn C, Jennings K, Rubenstein JL. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development. 2001;128:353–363. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases