PMID:15464571

Citation	Hellard, D, Brosenitsch, T, Fritzsch, B and Katz, DM (2004) Cranial sensory neuron development in the absence of brain-derived neurotrophic factor in BDNF/Bax double null mice. Dev. Biol. 275:34-43
Abstract	To investigate the role of brain-derived neurotrophic factor (BDNF) in differentiation of cranial sensory neurons in vivo, we analyzed development of nodose (NG), petrosal (PG), and vestibular (VG) ganglion cells in genetically engineered mice carrying null mutations in the genes encoding BDNF and the proapoptotic Bcl-2 homolog Bax. In bax(-/-) mutants, ganglion cell numbers were increased significantly compared to wild-type animals, indicating that naturally occurring cell death in these ganglia is regulated by Bax signaling. Analysis of bdnf(-/-)bax(-/-) mutants revealed that, although the Bax null mutation completely rescued cell loss in the absence of BDNF, it did not rescue the lethality of the BDNF null phenotype. Moreover, despite rescue of BDNF-dependent neurons by the bax null mutation, sensory target innervation was abnormal in double null mutants. Vagal sensory innervation to baroreceptor regions of the cardiac outflow tract was completely absent, and the density of vestibular sensory innervation to the cristae organs was markedly decreased, compared to wild-type controls. Moreover, vestibular afferents failed to selectively innervate their hair cell targets within the cristae organs in the double mutants. These innervation failures occurred despite successful navigation of sensory fibers to the peripheral field, demonstrating that BDNF is required locally for afferent ingrowth into target tissues. In addition, the bax null mutation failed to rescue expression of the dopaminergic phenotype in a subset of NG and PG neurons. These data demonstrate that BDNF signaling is required not only to support survival of cranial sensory neurons, but also to regulate local growth of afferent fibers into target tissues and, in some cells, transmitter phenotypic expression is required.
Links	PubMed Online version:10.1016/j.ydbio.2004.07.021
Keywords	Animals; Brain-Derived Neurotrophic Factor/deficiency; Brain-Derived Neurotrophic Factor/genetics; Cell Survival/physiology; Ganglia, Sensory/embryology; Ganglia, Sensory/metabolism; Mice; Mice, Transgenic; Neurons, Afferent/metabolism; Pressoreceptors/metabolism; Proto-Oncogene Proteins c-bcl-2/deficiency; Proto-Oncogene Proteins c-bcl-2/genetics; Subclavian Artery/innervation; Vestibule, Labyrinth/innervation; bcl-2-Associated X Protein
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