PMID- 24378336 OWN - NLM STAT- MEDLINE DCOM- 20140326 LR - 20211021 IS - 1095-564X (Electronic) IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 386 IP - 2 DP - 2014 Feb 15 TI - BDNF and NT4 play interchangeable roles in gustatory development. PG - 308-20 LID - S0012-1606(13)00693-3 [pii] LID - 10.1016/j.ydbio.2013.12.031 [doi] AB - A limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. The gustatory system is ideal for examining this issue because the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles although both of them activate the same receptors, TrkB and p75. Here we first investigated whether the different roles of BDNF and NT4 are due to their differences in temporal and spatial expression patterns. Then, we asked whether or not these two neurotrophins exert their unique roles on the gustatory system by regulating different sets of downstream genes. By using Bdnf(Nt4/Nt4) mice, in which the coding region for BDNF is replaced with NT4, we examined whether the different functions of BDNF and NT4 are interchangeable during taste development. Our results demonstrated that NT4 could mediate most of the unique roles of BDNF during taste development. Specifically, caspase-3-mediated cell death, which was increased in the geniculate ganglion in Bdnf(-/-) mice, was rescued in Bdnf(Nt4/Nt4) mice. In BDNF knockout mice, tongue innervation was disrupted, and gustatory axons failed to reach their targets. However, disrupted innervation was rescued and target innervation is normal when NT4 replaced BDNF. Genome wide expression analyses revealed that BDNF and NT4 mutant mice exhibited different gene expression profiles in the gustatory (geniculate) ganglion. Compared to wild type, the expression of differentiation-, apoptosis- and axon guidance-related genes was changed in BDNF mutant mice, which is consistent with their different roles during taste development. However, replacement of BDNF by NT4 rescued these gene expression changes. These findings indicate that the functions of BDNF and NT4 in taste development are interchangeable. Spatial and temporal differences in BDNF and NT4 expression can regulate differential gene expression in vivo and determine their specific roles during development. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Huang, Tao AU - Huang T AD - Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40292, USA. FAU - Krimm, Robin F AU - Krimm RF AD - Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40292, USA. Electronic address: rfkrim01@louisville.edu. LA - eng GR - R01 DC007176/DC/NIDCD NIH HHS/United States GR - R01 DC009418/DC/NIDCD NIH HHS/United States GR - DC007176/DC/NIDCD NIH HHS/United States GR - DC009418/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131227 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (1,1'-dioleyl-3,3,3',3'-tetramethylindocarbocyanine) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbocyanines) RN - 0 (Nerve Growth Factors) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Carbocyanines MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental/genetics/*physiology MH - Geniculate Ganglion/metabolism MH - Immunohistochemistry MH - Laser Capture Microdissection MH - Mice MH - Mice, Knockout MH - Microarray Analysis MH - Nerve Growth Factors/genetics/*metabolism MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Taste/*physiology PMC - PMC3950349 MID - NIHMS558366 OTO - NOTNLM OT - Brain derived neurotrophic factor OT - Geniculate ganglion neurons OT - Neurotrophin-4 OT - Neurotrophins OT - Taste EDAT- 2014/01/01 06:00 MHDA- 2014/03/29 06:00 PMCR- 2015/02/15 CRDT- 2014/01/01 06:00 PHST- 2013/10/02 00:00 [received] PHST- 2013/12/17 00:00 [revised] PHST- 2013/12/20 00:00 [accepted] PHST- 2014/01/01 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2014/03/29 06:00 [medline] PHST- 2015/02/15 00:00 [pmc-release] AID - S0012-1606(13)00693-3 [pii] AID - 10.1016/j.ydbio.2013.12.031 [doi] PST - ppublish SO - Dev Biol. 2014 Feb 15;386(2):308-20. doi: 10.1016/j.ydbio.2013.12.031. Epub 2013 Dec 27.