The neurotrophin receptor p75 regulates gustatory axon branching and promotes innervation of the tongue during development

Neural Development

Robin F Krimm¹  Tao Huang¹  Da Fei¹ 

[1] Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40292, USA

关键词: TrkB;    Neurotrophins;    p75;    Gustatory;    Taste;   

Others  :  802287
DOI  :  10.1186/1749-8104-9-15

 received in 2014-02-24, accepted in 2014-05-28,  发布年份 2014

【 摘 要 】

Background

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) regulate the survival of gustatory neurons, axon growth and branching, and innervation of taste buds during development. These actions are largely, but not completely, mediated through the tyrosine kinase receptor, TrkB. Here, we investigated the role of p75, the other major receptor for BDNF and NT4, in the development of the taste system.

Results

We found that p75^−/−mice showed delayed axon outgrowth and reduced branching of gustatory axons at embryonic day (E)13.5. From E14.5 to E18.5, gustatory neurons innervated fewer papillae and completely failed to innervate the mid-region of the tongue in p75^−/−mice. These early effects of the p75 mutation on gustatory axons preceded the loss of geniculate ganglion neurons starting at E14.5 and also contributed to a loss of taste buds at and after birth. Because knockouts for the TrkB receptor (TrkB^−/−) do not lose as many taste buds as hybrid knockouts for its two ligands (BDNF and NT4), we asked if p75 maintains those additional taste buds in the absence of TrkB. It does not; hybrid TrkB^−/−/p75^−/−mice had more taste buds than TrkB^−/−mice; these additional taste buds were not due to an increase in neurons or innervation.

Conclusions

p75 regulates gustatory neuron axon branching and tongue innervation patterns during taste system development. This function is likely accomplished independently of BDNF, NT4, and TrkB. In addition, p75 does not support the remaining neurons or taste buds in TrkB^−/−mice.

【 授权许可】

   
2014 Fei et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]Mbiene JP, Mistretta CM: Initial innervation of embryonic rat tongue and developing taste papillae: nerves follow distinctive and spatially restricted pathways. Acta Anat (Basel) 1997, 160:139-158.
• [2]Lopez GF, Krimm RF: Refinement of innervation accuracy following initial targeting of peripheral gustatory fibers. J Neurobiol 2006, 66:1033-1043.
• [3]Krimm RF, Hill DL: Innervation of single fungiform taste buds during development in rat. J Comp Neurol 1998, 398:13-24.
• [4]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 M, Yancopoulos GD: Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature 1995, 375:235-238.
• [5]Patel AV, Krimm RF: BDNF is required for the survival of differentiated geniculate ganglion neurons. Dev Biol 2010, 340:419-429.
• [6]Hoshino N, Vatterott P, Egwiekhor A, Rochlin MW: Brain-derived neurotrophic factor attracts geniculate ganglion neurites during embryonic targeting. Dev Neurosci 2010, 32:184-196.
• [7]Lopez GF, Krimm RF: Epithelial overexpression of BDNF and NT4 produces distinct gustatory axon morphologies that disrupt initial targeting. Dev Biol 2006, 292:457-468.
• [8]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, 29:3354-3364.
• [9]Ringstedt T, Ibanez CF, Nosrat CA: Role of brain-derived neurotrophic factor in target invasion in the gustatory system. J Neurosci 1999, 19:3507-3518.
• [10]Liu X, Ernfors P, Wu H, Jaenisch R: Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 1995, 375:238-241.
• [11]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, 365:50-60.
• [12]Huang T, Krimm RF: Developmental expression of Bdnf, Ntf4/5, and TrkB in the mouse peripheral taste system. Dev Dyn 2010, 239:2637-2646.
• [13]Huang T, Krimm RF: BDNF and NT4 play interchangeable roles in gustatory development. Dev Biol 2014, 386:308-320.
• [14]Berkemeier LR, Winslow JW, Kaplan DR, Nikolics K, Goeddel DV, Rosenthal A: Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron 1991, 7:857-866.
• [15]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, 15:563-576.
• [16]Klein R, Nanduri V, Jing SA, Lamballe F, Tapley P, Bryant S, Cordon-Cardo C, Jones KR, Reichardt LF, Barbacid M: The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell 1991, 66:395-403.
• [17]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:e83460.
• [18]Krimm RF: Mice lacking the p75 receptor fail to acquire a normal complement of taste buds and geniculate ganglion neurons by adulthood. Anat Rec A Discov Mol Cell Evol Biol 2006, 288:1294-1302.
• [19]Blochl A, Blochl R: A cell-biological model of p75NTR signaling. J Neurochem 2007, 102:289-305.
• [20]Chao MV: The p75 neurotrophin receptor. J Neurobiol 1994, 25:1373-1385.
• [21]DeFreitas MF, McQuillen PS, Shatz CJ: A novel p75NTR signaling pathway promotes survival, not death, of immunopurified neocortical subplate neurons. J Neurosci 2001, 21:5121-5129.
• [22]Hempstead BL: The many faces of p75NTR. Curr Opin Neurobiol 2002, 12:260-267.
• [23]Lopez-Sanchez N, Frade JM: Control of the cell cycle by neurotrophins: lessons from the p75 neurotrophin receptor. Histol Histopathol 2002, 17:1227-1237.
• [24]Roux PP, Barker PA: Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 2002, 67:203-233.
• [25]Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL: ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci 2005, 25:5455-5463.
• [26]Yamashita T, Fujitani M, Hata K, Mimura F, Yamagishi S: Diverse functions of the p75 neurotrophin receptor. Anat Sci Int 2005, 80:37-41.
• [27]Mistretta CM, Hill DL: Development of the taste system: basic neurobiology. In Handbook of Olfaction and Gustation. Edited by RichardL D. New York: Marcel Dekker; 2003:759-782.
• [28]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, 409:13-24.
• [29]Nosrat CA, Blomlof J, ElShamy WM, Ernfors P, Olson L: Lingual deficits in BDNF and NT3 mutant mice leading to gustatory and somatosensory disturbances, respectively. Development 1997, 124:1333-1342.
• [30]Sun H, Oakley B: Development of anterior gustatory epithelia in the palate and tongue requires epidermal growth factor receptor. Dev Biol 2002, 242:31-43.
• [31]Hosley MA, Hughes SE, Morton LL, Oakley B: A sensitive period for the neural induction of taste buds. J Neurosci 1987, 7:2075-2080.
• [32]Whitehead MC, Kachele DL: Development of fungiform papillae, taste buds, and their innervation in the hamster. J Comp Neurol 1994, 340:515-530.
• [33]Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD: The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 1998, 140:911-923.
• [34]Deppmann CD, Mihalas S, Sharma N, Lonze BE, Niebur E, Ginty DD: A model for neuronal competition during development. Science 2008, 320:369-373.
• [35]Farinas I, Wilkinson GA, Backus C, Reichardt LF, Patapoutian A: Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo. Neuron 1998, 21:325-334.
• [36]Rochlin MW, Farbman AI: Trigeminal ganglion axons are repelled by their presumptive targets. J Neurosci 1998, 18:6840-6852.
• [37]Rochlin MW, O'Connor R, Giger RJ, Verhaagen J, Farbman AI: Comparison of neurotrophin and repellent sensitivities of early embryonic geniculate and trigeminal axons. J Comp Neurol 2000, 422:579-593.
• [38]Runge EM, Hoshino N, Biehl MJ, Ton S, Rochlin MW: Neurotrophin-4 is more potent than brain-derived neurotrophic factor in promoting, attracting and suppressing geniculate ganglion neurite outgrowth. Dev Neurosci 2012, 34(5):389-401.
• [39]Bentley CA, Lee KF: p75 is important for axon growth and Schwann cell migration during development. J Neurosci 2000, 20:7706-7715.
• [40]Lim YS, McLaughlin T, Sung TC, Santiago A, Lee KF, O'Leary DD: p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping. Neuron 2008, 59:746-758.
• [41]Ben-Zvi A, Ben-Gigi L, Klein H, Behar O: Modulation of semaphorin3A activity by p75 neurotrophin receptor influences peripheral axon patterning. J Neurosci 2007, 27:13000-13011.
• [42]Vilbig R, Cosmano J, Giger R, Rochlin MW: Distinct roles for Sema3A, Sema3F, and an unidentified trophic factor in controlling the advance of geniculate axons to gustatory lingual epithelium. J Neurocytol 2004, 33:591-606.
• [43]Dillon TE, Saldanha J, Giger R, Verhaagen J, Rochlin MW: Sema3A regulates the timing of target contact by cranial sensory axons. J Comp Neurol 2004, 470:13-24.
• [44]Perrelet D, Ferri A, Liston P, Muzzin P, Korneluk RG, Kato AC: IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo. Nat Cell Biol 2002, 4:175-179.
• [45]Lee KF, Li E, Huber LJ, Landis SC, Sharpe AH, Chao MV, Jaenisch R: Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system. Cell 1992, 69:737-749.
• [46]Sorensen B, Tandrup T, Koltzenburg M, Jakobsen J: No further loss of dorsal root ganglion cells after axotomy in p75 neurotrophin receptor knockout mice. J Comp Neurol 2003, 459:242-250.
• [47]Stucky CL, Koltzenburg M: The low-affinity neurotrophin receptor p75 regulates the function but not the selective survival of specific subpopulations of sensory neurons. J Neurosci 1997, 17:4398-4405.
• [48]Frade JM, Rodriguez-Tebar A, Barde YA: Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 1996, 383:166-168.
• [49]Nikoletopoulou V, Lickert H, Frade JM, Rencurel C, Giallonardo P, Zhang L, Bibel M, Barde YA: Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 2010, 467:59-63.
• [50]Guagliardo NA, Hill DL: Fungiform taste bud degeneration in C57BL/6 J mice following chorda-lingual nerve transection. J Comp Neurol 2007, 504:206-216.
• [51]Guth L: The effects of glossopharyngeal nerve transection on the circumvallate papilla of the rat. Anat Rec 1957, 128:715-731.
• [52]Naga IA, Sakla FB, Girgis ZA, State FA: Denervation of taste buds in the rabbit. Am J Anat 1970, 129:53-63.
• [53]Nagato T, Matsumoto K, Tanioka H, Kodama J, Toh H: Effect of denervation on morphogenesis of the rat fungiform papilla. Acta Anat (Basel) 1995, 153:301-309.
• [54]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, 518:3290-3301.
• [55]Whitehead MC, Frank ME, Hettinger TP, Hou LT, Nah HD: Persistence of taste buds in denervated fungiform papillae. Brain research 1987, 405:192-195.
• [56]Hosley MA, Oakley B: Postnatal development of the vallate papilla and taste buds in rats. Anat Rec 1987, 218:216-222.
• [57]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.
• [58]Ito A, Nosrat CA: Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4. Cell Tissue Res 2009, 337:349-359.
• [59]Abercrombie M: Estimation of nuclear population from microtome sections. Anat Rec 1946, 94:239-247.
• [60]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.
• [61]Liebl DJ, Mbiene JP, Parada LF: NT4/5 mutant mice have deficiency in gustatory papillae and taste bud formation. Dev Biol 1999, 213:378-389.
• [62]Finger TE, Danilova V, Barrows J, Bartel DL, Vigers AJ, Stone L, Hellekant G, Kinnamon SC: ATP signaling is crucial for communication from taste buds to gustatory nerves. Science 2005, 310:1495-1499.
• [63]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.
• [64]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, 232:508-521.