Establishment and controlled differentiation of neural crest stem cell lines using conditional transgenesis

doi:10.1111/j.1432-0436.2007.00164.x

Differentiation

Volume 75, Issue 7, September 2007, Pages 580-591

https://doi.org/10.1111/j.1432-0436.2007.00164.x Get rights and content

Abstract

Murine neural crest stem cells (NCSCs) are a multipotent transient population of stem cells. After being formed during early embryogenesis as a consequence of neurulation at the apical neural fold, the cells rapidly disperse throughout the embryo, migrating along specific pathways and differentiating into a wide variety of cell types. In vitro the multipotency is lost rapidly, making it difficult to study differentiation potential as well as cell fate decisions. Using a transgenic mouse line, allowing for spatio-temporal control of the transforming c-myc oncogene, we derived a cell line (JoMa1), which expressed NCSC markers in a transgene-activity dependent manner. JoMa1 cells express early NCSC markers and can be instructed to differentiate into neurons, glia, smooth muscle cells, melanocytes, and also chondrocytes. A cell-line, clonally derived from JoMa1 culture, termed JoMa1.3 showed identical behavior and was studied in more detail. This system therefore represents a powerful tool to study NCSC biology and signaling pathways. We observed that when proliferative and differentiation stimuli were given, enhanced cell death could be detected, suggesting that the two signals are incompatible in the cellular context. However, the cells regain their differentiation potential after inactivation of c-MycER^T. In summary, we have established a system, which allows for the biochemical analysis of the molecular pathways governing NCSC biology. In addition, we should be able to obtain NCSC lines from crossing the c-MycER^T mice with mice harboring mutations affecting neural crest development enabling further insight into genetic pathways controlling neural crest differentiation.

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ORIGINAL ARTICLEEstablishment and controlled differentiation of neural crest stem cell lines using conditional transgenesis

Abstract

Cancer Lett

Dev Cell

Neuron

Neuron

Dev Biol

Dev Biol

Dev Biol

J Biol Chem

Neuron

Neuron

Neuron

Curr Biol

Cell

Mol Cell

Cell

Cell

Int Rev Cytol

Dev Biol

Neuron

Cell

Dev Biol

Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors

Proc Natl Acad Sci USA

Cell lineage determination and the control of neuronal identity in the neural crest

Cold Spring Harb Symp Quant Biol

Clone-forming ability and differentiation potential of migratory neural crest cells

Proc Natl Acad Sci USA

Timing and competence of neural crest formation

Dev Neurosci

Neural crest cell formation and migration in the developing embryo

Faseb J

Cell lineage analysis reveals multipotency of some avian neural crest cells

Nature

Cell lineage analysis of the avian neural crest

Development

Transforming growth factor-beta-induced differentiation of smooth muscle from a neural crest stem cell line

Circ Res

Environmental signals and cell fate specification in premigratory neural crest

Bioessays

ORIGINAL ARTICLE
Establishment and controlled differentiation of neural crest stem cell lines using conditional transgenesis