0000000000199886
AUTHOR
Elena Bellmunt
Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells.
Chromosome integrity is essential for cell viability and, therefore, highly proliferative cell types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results in growth impairments in all highly proliferative cell populations analyzed so far. We show that telomere attrition dramatically impairs the in vitro proliferation of adult neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of telomerase-deficient adult mice. Reduced proliferation of postnatal neurogenic progenitors was also observed in vivo, in the absence of exogenous mitogenic stimulation. Strikingly, severe telo…
Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor
During the development of peripheral ganglia, 50% of the neurons that are generated undergo apoptosis. How the massive numbers of corpses are removed is unknown. We found that satellite glial cell precursors are the primary phagocytic cells for apoptotic corpse removal in developing mouse dorsal root ganglia (DRG). Confocal and electron microscopic analysis revealed that glial precursors, rather than macrophages, were responsible for clearing most of the dead DRG neurons. Moreover, we identified Jedi-1, an engulfment receptor, and MEGF10, a purported engulfment receptor, as homologs of the invertebrate engulfment receptors Draper and CED-1 expressed in the glial precursor cells. Expression …
Erbb2 regulates neuromuscular synapse formation and is essential for muscle spindle development
Neuregulins and their Erbb receptors have been implicated in neuromuscular synapse formation by regulating gene expression in subsynaptic nuclei. To analyze the function of Erbb2 in this process, we have inactivated the Erbb2 gene in developing muscle fibers by Cre/Lox-mediated gene ablation. Neuromuscular synapses form in the mutant mice, but the synapses are less efficient and contain reduced levels of acetylcholine receptors. Surprisingly, the mutant mice also show proprioceptive defects caused by abnormal muscle spindle development. Sensory Ia afferent neurons establish initial contact with Erbb2-deficient myotubes. However, functional spindles never develop. Taken together, our data su…
Regulation of neurogenesis by neurotrophins in developing spinal sensory ganglia.
Neurons and glia in spinal sensory ganglia derive from multipotent neural crest-derived stem cells. In contrast to neural progenitor cells in the central nervous system, neural crest progenitors coexist with differentiated sensory neurons all throughout the neurogenic period. Thus, developing sensory ganglia are advantageous for determining the possible influence of cell-cell interactions in the regulation of precursor proliferation and neurogenesis. Neurotrophins are important regulators of neuronal survival in the developing vertebrate nervous system and, in addition, they appear to influence precursor behavior in vitro. Studies in mice carrying mutations in neurotrophin genes provide a g…