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During vertebrate development, neuronal survival depends on target-derived neurotrophic factors. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, can prevent the death of particular peripheral sensory neurons in vitro, and of central motor neurons as well as dopaminergic and cholinergic neurons of the basal forebrain during(More)
Neurotrophin-3-deficient (NT-3-deficient) mice were generated by gene targeting. Mutant mice displayed severe movement defects of the limbs, and most died shortly after birth. Substantial portions of peripheral sensory and sympathetic neurons were lost while motor neurons were not affected. Significantly, spinal proprioceptive afferents and their peripheral(More)
We have generated mice carrying a mutation of the gene encoding the low affinity NGF receptor p75NGFR by targeted mutation in embryonic stem cells. Mice homozygous for the mutation were viable and fertile. Immunohistochemical analyses of the footpad skin of mutant mice revealed markedly decreased sensory innervation by calcitonin gene-related peptide- and(More)
This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes.(More)
The role of the common low affinity neurotrophin receptor, p75, is controversial. Studies using cell lines suggest that p75 is either essential or dispensable for neurotrophin responsiveness. To resolve this issue, we studied the survival response of developing neurons obtained from normal mouse embryos and embryos with a null mutation in the p75 gene.(More)
During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others' function in the developing cerebral cortex, we examined the role of glial growth factor (a(More)
To understand the role of low-affinity neurotrophin receptor p75 in neural development, we previously generated mice carrying a null mutation in the p75 locus (Lee, K. F., Li, E., Huber, L. J., Landis, S. C., Sharpe, A. H., Chao, M. V. and Jaenisch, R. (1992) Cell 69, 737-749). To elucidate the mechanisms leading to deficits in the peripheral nervous system(More)
The neurotrophin receptor p75 is a low-affinity receptor that binds neurotrophins. To investigate the role of p75 in the survival and function of central neurons, p75 null-mutant and wild type litter mate mice were tested on behavioral tasks. Null mutants showed significant performance deficits on water maze, inhibitory avoidance, motor activity, and(More)
The development of Schwann cells, the myelin-forming glial cells of the vertebrate peripheral nervous system, involves a neonatal phase of proliferation in which cells migrate along and segregate newly formed axons. Withdrawal from the cell cycle, around postnatal days 2-4 in rodents, initiates terminal differentiation to the myelinating state. During this(More)
The low-affinity neurotrophin receptor p75 binds all neurotrophins with similar affinity. For elucidation of its function, mice bearing a null mutation in the p75 locus were generated. Examination of sympathetic innervation of target tissues revealed that pineal glands lacked innervation and sweat gland innervation was absent or reduced in particular(More)