NT-3 and CNTF exert dose-dependent, pleiotropic effects on cells in the immature dorsal root ganglion: neuregulin-mediated proliferation of progenitor cells and neuronal differentiation.

Neurons in the nascent dorsal root ganglia are born and differentiate in a complex cellular milieu composed of postmitotic neurons, and mitotically active glial and neural progenitor cells. Neurotrophic factors such as NT-3 are critically important for promoting the survival of postmitotic neurons in the DRG. However, the factors that regulate earlier events in the development of the DRG such as the mitogenesis of DRG progenitor cells and the differentiation of neurons are less defined.

PACAP promotes sensory neuron differentiation: blockade by neurotrophic factors.

Developing neurons encounter a panoply of extracellular signals as they differentiate. A major goal is to identify these extrinsic cues and define the mechanisms by which neurons simultaneously integrate stimulation by multiple factors yet initiate one specific biological response. Factors that are known to exert potent activities in the developing nervous system include the NGF family of neurotrophic factors, ciliary neurotrophic factor (CNTF), and pituitary adenylate cyclase-activating peptide (PACAP).

Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).

trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation.

4-hydroxynonenal inhibits Na(+)-K(+)-ATPase.

4-Hydroxynonenal binds rapidly to Na(+)-K(+)-ATPase, and this was accompanied by a decrease in measurable sulfhydryl groups and a loss of enzyme activity. The I50 value for Na(+)-K(+)-ATPase inhibition by 4-hydroxynonenal was found to be 120 microM. Although the sulfhydryl groups could be completely restored with beta-mercaptoethanol during the reaction of the Na(+)-K(+)-ATPase-HNE-adduct, the Na(+)-K(+)-ATPase activity was only partially restored by this reducing agent.

Expression of a novel nuclear protein is correlated with neuronal differentiation in vivo.

We report the production of a monoclonal antibody (MAb 526) that recognizes a novel, developmentally regulated nuclear protein expressed in neurons throughout the rat nervous system. Analysis of whole brain and cell nuclear extracts by SDS-PAGE and immunoblotting determined that MAb 526 recognizes a single nuclear protein (np) of apparent molecular weight 42 kD, designated np526, as well as a slightly larger (ca. 44 kD) cytoplasmic protein.