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Dev Dyn. 2013 Mar;242(3):230-53. doi: 10.1002/dvdy.23920. Epub 2013 Feb 8.

Expression of Neurogenin 1 in mouse embryonic stem cells directs the differentiation of neuronal precursors and identifies unique patterns of down-stream gene expression.

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1
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Abstract

BACKGROUND:

Delineating the cascades of growth and transcription factor expression that shape the developing nervous system will improve our understanding of its molecular histogenesis and suggest strategies for cell replacement therapies. In the current investigation, we examined the ability of the proneural gene, Neurogenin1 (Neurog1; also Ngn1, Neurod3), to drive differentiation of pluripotent embryonic stem cells (ESC).

RESULTS:

Transient expression of Neurog1 in ESC was sufficient to initiate neuronal differentiation, and produced neuronal subtypes reflecting its expression pattern in vivo. To begin to address the molecular mechanisms involved, we used microarray analysis to identify potential down-stream targets of Neurog1 expressed at sequential stages of neuronal differentiation.

CONCLUSIONS:

ESC expressing Neurogenin1 begin to withdraw from cycle and form precursors that differentiate exclusively into neurons. This work identifies unique patterns of gene expression following expression of Neurog1, including genes and signaling pathways involved in process outgrowth and cell migration, regional differentiation of the nervous system, and cell cycle.

PMID:
23288605
PMCID:
PMC4646168
DOI:
10.1002/dvdy.23920
[Indexed for MEDLINE]
Free PMC Article
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