Spinal cord neuronal precursors generate multiple neuronal phenotypes in culture.
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.
Kalyani
A J
AJ
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Piper
D
D
Mujtaba
T
T
Lucero
M T
MT
Rao
M S
MS
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002478:Cells, Cultured; D004627:Embryonic Induction / Q000502:physiology; D005110:Extracellular Space / Q000737:chemistry / Q000502:physiology; D005260:Female; D005333:Fetus / Q000166:cytology; D053823:Hedgehog Proteins; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000235:genetics / Q000494:pharmacology; D009500:Neutralization Tests; D010641:Phenotype; D011247:Pregnancy; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D015534:Trans-Activators; D016212:Transforming Growth Factor beta
D000906:Antibodies; C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D019006:Neural Cell Adhesion Molecules; D018377:Neurotransmitter Agents; D011506:Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta