BDNF is required for the survival of differentiated geniculate ganglion neurons.
In mice lacking functional brain-derived neurotrophic factor (BDNF), the number of geniculate ganglion neurons, which innervate taste buds, is reduced by one-half. Here, we determined how and when BDNF regulates the number of neurons in the developing geniculate ganglion. The loss of geniculate neurons begins at embryonic day 13.5 (E13.5) and continues until E18.5 in BDNF-null mice. Neuronal loss in BDNF-null mice was prevented by the removal of the pro-apoptotic gene Bax. Thus, BDNF regulates embryonic geniculate neuronal number by preventing cell death rather than promoting cell proliferation. The number of neurofilament positive neurons expressing activated caspase-3 increased on E13.5 in bdnf(-/-) mice, compared to wild-type mice, demonstrating that differentiated neurons were dying. The axons of geniculate neurons approach their target cells, the fungiform papillae, beginning on E13.5, at which time we found robust BDNF(LacZ) expression in these targets. Altogether, our findings establish that BDNF produced in peripheral target cells regulates the survival of early geniculate neurons by inhibiting cell death of differentiated neurons on E13.5 of development. Thus, BDNF acts as a classic target-derived growth factor in the developing taste system.
Patel
Ami V
AV
Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Louisville, KY 40202, USA.
Krimm
Robin F
RF
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000502:physiology; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D005830:Geniculate Ganglion / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D013650:Taste Buds / Q000196:embryology; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494827:Bax protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D051028:bcl-2-Associated X Protein; D053148:Caspase 3