期刊论文详细信息
Neural Development
Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system
Liliana Minichiello1  Chinnavuth Vatanashevanopakorn2  Jacqueline M Horn1  Juraj Koudelka3 
[1] Department of Pharmacology, University of Oxford, OX1 3QT Oxford, UK;Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;Centre for Neuroregeneration, University of Edinburgh, EH16 4SB Edinburgh, UK
关键词: Taste receptors;    Taste buds;    Survival;    Gustatory system;    TrkB signalling;    Neurotrophin-4;    Brain derived neurotrophic factor;   
Others  :  1146404
DOI  :  10.1186/1749-8104-9-21
 received in 2014-07-03, accepted in 2014-09-18,  发布年份 2014
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【 摘 要 】

Background

Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking.

Results

Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered.

Conclusions

We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment.

【 授权许可】

   
2014 Koudelka et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Fan G, Egles C, Sun Y, Minichiello L, Renger JJ, Klein R, Liu G, Jaenisch R: Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities. Nat Neurosci 2000, 3(4):350-357.
  • [2]Huang T, Krimm RF: BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol 2014, 386(2):308-320.
  • [3]Jones KR, Fariñas I, Backus C, Reichardt LF: Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell 1994, 76(6):989-999.
  • [4]Liu X, Ernfors P, Wu H, Jaenisch R: Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 1995, 375(6528):238-241.
  • [5]Patel AV, Krimm RF: BDNF is required for the survival of differentiated geniculate ganglion neurons. Dev Biol 2010, 340(2):419-429.
  • [6]Patel AV, Krimm RF: Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor. Dev Biol 2012, 365(1):50-60.
  • [7]Ma L, Lopez GF, Krimm RF: Epithelial-derived brain-derived neurotrophic factor is required for gustatory neuron targeting during a critical developmental period. J Neurosci 2009, 29(11):3354-3364.
  • [8]Fritzsch B, Sarai PA, Barbacid M, Silos-Santiago I: Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds. Int J Dev Neurosci 1997, 15(4–5):563-576.
  • [9]Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P, Friedman B, Wiegand S, Vejsada R, Kato AC, Dechiara TM, Yancopoulos GD: Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 1995, 375(6528):235-238.
  • [10]Fei D, Krimm RF: Taste neurons consist of both a large TrkB-receptor-dependent and a small TrkB-receptor-independent subpopulation. PLoS One 2013, 8(12):e83460.
  • [11]Huang EJ, Reichardt LF: Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 2003, 72:609-642.
  • [12]Minichiello L: TrkB signalling pathways in LTP and learning. Nat Rev Neurosci 2009, 10(12):850-860.
  • [13]Minichiello L, Casagranda F, Tatche RS, Stucky CL, Postigo A, Lewin GR, Davies AM, Klein R: Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses. Neuron 1998, 21(2):335-345.
  • [14]Minichiello L, Calella AM, Medina DL, Bonhoeffer T, Klein R, Korte M: Mechanism of TrkB-mediated hippocampal long-term potentiation. Neuron 2002, 36(1):121-137.
  • [15]Medina DL, Sciarretta C, Calella AM, Von Bohlen Und Halbach O, Unsicker K, Minichiello L: TrkB regulates neocortex formation through the Shc/PLCgamma-mediated control of neuronal migration. EMBO J 2004, 23(19):3803-3814.
  • [16]Jung HS, Akita K, Kim JY: Spacing patterns on tongue surface-gustatory papilla. Int J Dev Biol 2004, 48:157-161.
  • [17]Patel AV, Huang T, Krimm RF: Lingual and palatal gustatory afferents each depend on both BDNF and NT-4, but the dependence is greater for lingual than palatal afferents. J Comp Neurol 2010, 518(16):3290-3301.
  • [18]Krimm RF, Miller KK, Kitzman PH, Davis BM, Albers KM: Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue. Dev Biol 2001, 232(2):508-521.
  • [19]Ishida Y, Ugawa S, Ueda T, Yamada T, Shibata Y, Hondoh A, Inoue K, Yu Y, Shimada S: P2X(2)- and P2X(3)-positive fibers in fungiform papillae originate from the chorda tympani but not the trigeminal nerve in rats and mice. J Comp Neurol 2009, 514:131-144.
  • [20]Sollars SI, Smith PC, Hill DL: Time course of morphological alterations of fungiform papillae and taste buds following chorda tympani transection in neonatal rats. J Neurobiol 2002, 51:223-236.
  • [21]Mistretta CM, Goosens KA, Farinas I, Reichardt LF: Alterations in size, number, and morphology of gustatory papillae and taste buds in BDNF null mutant mice demonstrate neural dependence of developing taste organs. J Comp Neurol 1999, 409(1):13-24.
  • [22]Krimm RF, Barlow LA: Development of the taste system. In The Senses: A Comprehensive Reference. 4th edition. San Diego: Academic Press: Firestein S, Beauchkamp GS; 2008:157-182.
  • [23]Zaidi FN, Whitehead MC: Discrete innervation of murine taste buds by peripheral taste neurons. J Neurosci 2006, 26(32):8243-8253.
  • [24]Krimm RF, Hill DL: Innervation of single fungiform taste buds during development in rat. J Comp Neurol 1998, 398(1):13-24.
  • [25]Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS: The receptors and cells for mammalian taste. Nature 2006, 444:288-294.
  • [26]Yarmolinsky DA, Zuker CS, Ryba NJ: Common sense about taste: from mammals to insects. Cell 2009, 139:234-244.
  • [27]Knapp L, Lawton A, Oakley B, Wong L, Zhang C: Keratins as markers of differentiated taste cells of the rat. Differentiation 1995, 58:341-349.
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