Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of postnatal-but not embryonic-mouse dorsal root ganglion cells in vitro, despite the fact that its receptors are expressed at both ages. To understand this difference, we have performed an oligonucleotide microarray experiment. We found that several hundred genes were regulated between embryonic and postnatal stages, and that several important classes of genes were differentially regulated by GDNF treatment, including genes related to translation and to phenotypic specification and maturation. Interestingly, a set of genes related to cell adhesion, cytoskeleton and cellular morphology were consistently down-regulated by GDNF, suggesting a previously uncharacterized role for GDNF in repressing neurite growth and/or branching. This nuclear program initiated by GDNF was functionally confirmed in cultures of embryonic wild-type neurons sustained with nerve growth factor and in bax(-/-) neurons that survive in the absence of trophic support.
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http://dx.doi.org/10.1073/pnas.251548898 | DOI Listing |
Biomolecules
December 2024
Department of Anesthesiology and Perioperative Medicine, University of Rochester, 601 Elmwood Ave, Box 604, Rochester, NY 14620, USA.
Astrocytes play critical roles in supporting structural and metabolic homeostasis in the central nervous system (CNS). CNS injury leads to the development of a range of reactive phenotypes in astrocytes whose molecular determinants are poorly understood. Finding ways to modulate astrocytic injury responses and leverage a pro-recovery phenotype holds promise in treating CNS injury.
View Article and Find Full Text PDFPLoS One
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National Centre for Cell Science, Ganeshkhind, Pune, India.
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View Article and Find Full Text PDFPrecise regulation of the chromatin environment through post-translational histone modification modulates transcription and controls brain development. Not surprisingly, mutations in a large number of histone-modifying enzymes underlie complex brain disorders. In particular, the histone methyltransferase ASH1L modifies histone marks linked to transcriptional activation and has been implicated in multiple neuropsychiatric disorders.
View Article and Find Full Text PDFRNA Biol
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Department of Biological Sciences, University of Denver, Denver, CO, USA.
Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and is caused by mutations in the gene encoding the Fragile X messenger ribonucleoprotein (FMRP). FMRP is an evolutionarily conserved and neuronally enriched RNA-binding protein (RBP) with functions in RNA editing, RNA transport, and protein translation. Specific target RNAs play critical roles in neurodevelopment, including the regulation of neurite morphogenesis, synaptic plasticity, and cognitive function.
View Article and Find Full Text PDFEur Child Adolesc Psychiatry
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Department of Neurology, Linyi People's Hospital, 27 East Section of Jiefang Road Lanshan District, Linyi, 276000, Shandong, China.
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