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The Journal of Neuroscience, October 1, 1998, 18(19):7856-7868
Spinal Cord Neuronal Precursors Generate Multiple Neuronal
Phenotypes in Culture
Anjali J.
Kalyani2,
David
Piper1,
Tahmina
Mujtaba2,
Mary T.
Lucero1, and
Mahendra S.
Rao2
1 Department of Physiology, University of Utah, Salt
Lake City, Utah 84132, and 2 Department of Neurobiology and
Anatomy, University of Utah School of Medicine, Salt Lake City, Utah
84132
Neuronal restricted precursors (NRPs) ()
can generate multiple neurotransmitter phenotypes during maturation in
culture. Undifferentiated E-NCAM+ (embryonic neural cell
adhesion molecule) immunoreactive NRPs are mitotically active and
electrically immature, and they express only a subset of neuronal
markers. Fully mature cells are postmitotic, process-bearing cells that
are neurofilament-M and synaptophysin immunoreactive, and they
synthesize and respond to different subsets of neurotransmitter
molecules. Mature neurons that synthesize and respond to glycine,
glutamate, GABA, dopamine, and acetylcholine can be identified by
immunocytochemistry, RT-PCR, and calcium imaging in mass cultures.
Individual NRPs also generate heterogeneous progeny as assessed by
neurotransmitter response and synthesis, demonstrating the multipotent
nature of the precursor cells.
Differentiation can be modulated by sonic hedgehog (Shh) and bone
morphogenetic protein (BMP)-2/4 molecules. Shh acts as a mitogen
and inhibits differentiation (including cholinergic differentiation). BMP-2 and BMP-4, in contrast, inhibit cell division and promote differentiation (including cholinergic differentiation). Thus, a single
neuronal precursor cell can differentiate into multiple classes
of neurons, and this differentiation can be modulated by environmental
signals.
Key words:
E-NCAM; spinal cord development; neuroblasts; stem cells; Shh; BMP
Copyright © 1998 Society for Neuroscience 0270-6474/98/18197856-13$05.00/0
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