PMID- 11401409 OWN - NLM STAT- MEDLINE DCOM- 20010628 LR - 20161124 IS - 0012-1606 (Print) IS - 0012-1606 (Linking) VI - 232 IP - 2 DP - 2001 Apr 15 TI - Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue. PG - 508-21 AB - Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) are essential for the survival of geniculate ganglion neurons, which provide the sensory afferents for taste buds of the anterior tongue and palate. To determine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BDNF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpression of BDNF or NT4 caused a 93 and 140% increase, respectively, in the number of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in the dorsal midregion and ventral tip of the tongue. No alterations were observed in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many were small, poorly innervated, and lost postnatally. To explain the loss of nerve innervation to fungiform papillae, the facial nerve of developing animals was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons in BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innervation to filiform papillae was observed. In addition, some papillae that formed in transgenic mice had two taste buds (instead of one) and were frequently arranged in clusters of two or three papillae. These results indicate that target-derived BDNF and NT4 are not only survival factors for geniculate ganglion neurons, but also have important roles in regulating the development and spatial patterning of fungiform papilla and targeting of taste neurons to these sensory structures. CI - Copyright 2001 Academic Press. FAU - Krimm, R F AU - Krimm RF AD - Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, Lexington, Kentucky 40536-0298, USA. rkrimm@pop.uky.edu FAU - Miller, K K AU - Miller KK FAU - Kitzman, P H AU - Kitzman PH FAU - Davis, B M AU - Davis BM FAU - Albers, K M AU - Albers KM LA - eng GR - F32 DC000370/DC/NIDCD NIH HHS/United States GR - F32DC00370/DC/NIDCD NIH HHS/United States GR - NS33730/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - P658DCA9XD (neurotrophin 4) SB - IM MH - Animals MH - Animals, Newborn MH - Body Patterning/genetics MH - Brain-Derived Neurotrophic Factor/*genetics/*physiology MH - Cell Survival MH - Embryonic and Fetal Development/genetics MH - Epithelium/embryology/growth & development/metabolism MH - Gene Expression Regulation, Developmental MH - Mice MH - Mice, Transgenic MH - Nerve Growth Factors/*genetics/*physiology MH - Neurons/cytology MH - Taste Buds/*embryology/*growth & development MH - Tongue/embryology/growth & development/innervation EDAT- 2001/06/13 10:00 MHDA- 2001/06/29 10:01 CRDT- 2001/06/13 10:00 PHST- 2001/06/13 10:00 [pubmed] PHST- 2001/06/29 10:01 [medline] PHST- 2001/06/13 10:00 [entrez] AID - S0012-1606(01)90190-3 [pii] AID - 10.1006/dbio.2001.0190 [doi] PST - ppublish SO - Dev Biol. 2001 Apr 15;232(2):508-21. doi: 10.1006/dbio.2001.0190.