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BMC Developmental Biology

, 7:86

First Online: 18 July 2007Received: 08 February 2007Accepted: 18 July 2007

Abstract

BackgroundUnderstanding how lineage choices are made during embryonic stem ES cell differentiation is critical for harnessing strategies for controlled production of therapeutic somatic cell types for cell transplantation and pharmaceutical drug screens. The in vitro generation of dopaminergic neurons, the type of cells lost in Parkinson-s disease patients- brains, requires the inductive molecules sonic hedgehog and FGF8, or an unknown stromal cell derived inducing activity SDIA. However, the exact identity of the responding cells and the timing of inductive activity that specify a dopaminergic fate in neural stem-progenitors still remain elusive.

ResultsUsing ES cells carrying a neuroepithelial cell specific vital reporter Sox1-GFP and FACS purification of Sox1-GFP neural progenitors, we have investigated the temporal aspect of SDIA mediated dopaminergic neuron specification during ES cell differentiation. Our results establish that SDIA induces a dopaminergic neuron fate in nascent neural stem or progenitor cells at, or prior to, Sox1 expression and does not appear to have further instructive role or neurotrophic activity during late neuronal differentiation of neural precursors. Furthermore, we show that dopaminergic neurons could be produced efficiently in a monolayer differentiation paradigm independent of SDIA activity or exogenous signalling molecules. In this case, the competence for dopaminergic neuron differentiation is also established at the level of Sox1 expression.

ConclusionDopaminergic neurons are specified early during mouse ES cell differentiation. The subtype specification seems to be tightly linked with the acquisition of a pan neuroectoderm fate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-213X-7-86 contains supplementary material, which is available to authorized users.

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Autor: Malin Parmar - Meng Li

Fuente: https://link.springer.com/article/10.1186/1471-213X-7-86







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