PMID- 19295142 OWN - NLM STAT- MEDLINE DCOM- 20090413 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 29 IP - 11 DP - 2009 Mar 18 TI - Epithelial-derived brain-derived neurotrophic factor is required for gustatory neuron targeting during a critical developmental period. PG - 3354-64 LID - 10.1523/JNEUROSCI.3970-08.2009 [doi] AB - Brain-derived neurotrophic factor (BDNF) is expressed in epithelial targets of gustatory neurons (i.e., fungiform papillae) before their innervation, and BDNF overexpression in nontaste regions of the tongue misdirects gustatory axons to these sites, suggesting that BDNF is necessary for gustatory axons to locate and innervate their correct targets during development. To test this hypothesis, we examined the targeting of taste neurons in BDNF-null mice (bdnf(-/-)). Analysis of bdnf(-/-) mice using a combination of DiI labeling and electron microscopy revealed that taste regions were not innervated by gustatory axons. Instead, branching was increased and many nontaste regions were innervated. The increased branching by gustatory axons in these animals was facilitated by neurotrophin 4 (NT4), because branching was virtually eliminated in bdnf(-/-)/nt4(-/-) mice. No abnormalities in gustatory innervation patterns and targeting were observed in nt4(-/-) mice. Conditional removal of BDNF selectively in epithelial cells disrupted targeting at the tongue tip, where gene recombination removed bdnf by embryonic day 13.5 (E13.5). However, innervation patterns were normal in the midregion and caudal portions of the tongue, where gene recombination did not occur until E14.5. These findings demonstrate that BDNF derived from gustatory epithelia is required for gustatory axons to correctly locate and innervate fungiform papillae. In addition, they show that BDNF-mediated targeting is restricted to a critical period of development, on or before E13.5. FAU - Ma, Liqun AU - Ma L AD - Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA. FAU - Lopez, Grace F AU - Lopez GF FAU - Krimm, Robin F AU - Krimm RF LA - eng GR - R01 DC007176-02/DC/NIDCD NIH HHS/United States GR - R01 DC007176-04/DC/NIDCD NIH HHS/United States GR - R01 DC007176-01/DC/NIDCD NIH HHS/United States GR - R01 DC007176-05/DC/NIDCD NIH HHS/United States GR - R01 DC007176-03/DC/NIDCD NIH HHS/United States GR - DC007176/DC/NIDCD NIH HHS/United States GR - R01 DC007176/DC/NIDCD NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*physiology MH - Epithelial Cells/cytology/*physiology MH - Female MH - Gene Expression Regulation, Developmental/*physiology MH - Gene Targeting/methods MH - Mice MH - Mice, Knockout MH - Neurons/cytology/*physiology MH - Pregnancy MH - Taste/physiology MH - Taste Buds/cytology/*embryology/*physiology MH - Tongue/cytology/embryology/physiology PMC - PMC2683425 MID - NIHMS103410 EDAT- 2009/03/20 09:00 MHDA- 2009/04/14 09:00 PMCR- 2009/09/18 CRDT- 2009/03/20 09:00 PHST- 2009/03/20 09:00 [entrez] PHST- 2009/03/20 09:00 [pubmed] PHST- 2009/04/14 09:00 [medline] PHST- 2009/09/18 00:00 [pmc-release] AID - 29/11/3354 [pii] AID - 3462637 [pii] AID - 10.1523/JNEUROSCI.3970-08.2009 [doi] PST - ppublish SO - J Neurosci. 2009 Mar 18;29(11):3354-64. doi: 10.1523/JNEUROSCI.3970-08.2009.