Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Development of Gustatory Organs and Innervating Sensory Ganglia
1 Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI, USA, 2 Institute for Biomedical Research, Kaunas University of Medicine, Kaunas, Lithuania and Department of Physics, Mathematics and Biophysics, Kaunas University of Medicine, Kaunas, Lithuania
Correspondence to be sent to: Charlotte M. Mistretta, e-mail: chmist{at}umich.edu
Key words: fungiform papilla, geniculate ganglion, neurotrophins, sonic hedgehog, taste, trigeminal ganglion
 |
Introduction |
|---|
 Top Introduction Peripheral target organs: tongue...Sensory ganglia: the geniculate...References |
|---|
Taste function requires neural circuits to transmit gustatory information from taste receptor cells in taste buds, via afferent nerves to the soma of ganglion neurons, and through central ganglion processes into the brainstem. During initial formation, the sensory ganglion neurons have a key situation in establishing receptive fields by extending neurites bidirectionally, to the peripheral taste organs and to central taste nuclei.
Our laboratory is studying functional differentiation of sensory ganglia that
innervate the tongue, and morphogenesis and patterning of the tongue and papilla organs.
The lingual ganglia and taste papillae initially develop independently, but then become
reciprocally dependent as ganglia derive molecular support from gustatory papillae and
the papillae require sensory innervation for growth and morphogenesis (Mistretta, 1998
). Currently our focus is on the
geniculate and trigeminal ganglia, which innervate anterior tongue, and the fungiform
papilla taste organs innervated by these ganglia. Geniculate and trigeminal ganglia
innervate spatially contiguous, but functionally distinct, sensory organs of the
fungiform papilla: the trigeminal neurons innervate lateral papilla epithelium and
subserve somatosensation and nociception, whereas the geniculate axons project to central
apical papilla epithelium to innervate cells that will form taste buds for gustatory
sensation (Mistretta and Hill,
2003).
In this brief paper we summarize some recent work on development of tongue and taste regions, and on early functional phenotypes of the geniculate and trigeminal ganglia.
|
Peripheral target organs: tongue and taste papillae |
|---|
|
TopIntroductionPeripheral target organs: tongue...Sensory ganglia: the geniculate...References |
|---|
The embryonic rat tongue goes through a series of morphological changes from E12 through E19, as the tongue appears as separate tissue swellings on the floor of the developing mandible, and progresses through gustatory papilla acquisition to final filiform papilla emergence (Mistretta, 1972
;
Mbiene et al., 1997). Using
in vitro approaches we have shown that the papillae develop independently of
sensory innervation (Mbiene et al.,
1997). However, by embryonic day 16 of the 21 day rat gestation, the papillae
are well-formed and robustly innervated by chorda tympani (from the geniculate ganglion)
and lingual (from the trigeminal) nerves (Mbiene
and Mistretta, 1997).
Because nerves are not essential for taste papilla initiation, we turned to study of
molecular regulators and hypothesized a role for the morphogen, sonic hedgehog (Shh)
(Ingham and McMahon, 2001), in target
organ development. With immunoreactions we have found an initial diffuse distribution of
Shh in early tongue swellings, and then a close association with papilla placodes (E14)
and the formed taste papillae (E15–16) (Liu
et al., 2004).
To determine functional roles for Shh in papilla development, we used whole tongue
cultures in which fungiform papillae develop with temporal and spatial distributions that
match formation in the embryo (Nosrat et
al., 2001;
Mistretta et al., 2003).
Cyclopamine, a steroid alkaloid that specifically disrupts Shh signaling at the receptor,
was added to cultures initiated at different stages of tongue or papilla development
(Liu et al., 2004). Blocking
Shh signaling had widely variant functional effects, including abrogation of tongue
formation (E12 cultures); alteration of fungiform papilla size and pattern (E13); and,
papilla pattern disruption including fungiform papilla formation on posterior tongue in
typically papilla-free regions (E14) (Figure
1). Furthermore, in cultures begun at
E16 there were no apparent effects of Shh signal disruption. Shh has, therefore, crucial
and stage-specific functions in tongue and taste papilla development.
|
Epidermal growth factor (EGF) and its receptor (EGFR) are immunolocalized in specific lingual locations that contrast with Shh during tongue and papilla development (Liu and Mistretta, 2004
). Adding EGF
to tongue cultures decreased the number of fungiform papillae, in a dose dependent
manner. Pre-incubation with EGF, followed by culture with EGF plus cyclopamine, prevented
the cyclopamine-induced change in papilla pattern. In summary, our data demonstrate roles for Shh and EGF in papilla development and patterning, and suggest interactions between these proteins in regulating papilla development. This is just the beginning of identifying the cast of molecules that regulate morphogenesis of the papilla epithelium—the epithelium that eventually differentiates at apical portions into taste cells, after nerves penetrate through basal lamina and initiate synapse formation.
|
Sensory ganglia: the geniculate and trigeminal |
|---|
|
TopIntroductionPeripheral target organs: tongue...Sensory ganglia: the geniculate...References |
|---|
Neurites growing from the geniculate and trigeminal ganglia require precise controls to establish innervation patterns in the fungiform papillae and specific functional properties. We used an explant system of the entire embryonic geniculate or trigeminal ganglion maintained in culture for several days and made whole cell recordings from single ganglion neurons (Grigaliunas et al., 2002
) (Figure
2). Trigeminal explants were
maintained with nerve growth factor (NGF) and geniculate ganglia with brain-derived
growth factor (BDNF) to maximally support neuron survival (Al-Hadlaq et al., 2003). Ganglia were dissected at
E16, when ganglion soma extend neurites to provide robust innervation of the early
fungiform papilla, or at E13, when neurites reach the early tongue but are not yet near
the epithelium of the lingual swellings (Mbiene
and Mistretta, 1997).
|
Comparing electrophysiological properties between E16 trigeminal and geniculate ganglion cells, geniculate neurons had smaller, shorter and sharper action potentials with lower thresholds than trigeminal neurons (Grigaliunas et al., 2002
). Whereas all trigeminal
neurons produced a single action potential at threshold depolarization, about 35%
of geniculate neurons fired repetitively. Further, all trigeminal neurons produced
tetrodotoxin (TTX)-resistant action potentials, but geniculate action potentials were
abolished in the presence of low concentrations of TTX (Figure
2).
Because the embryonic tongue and fungiform papillae express various neurotrophins
(Nosrat and Olson, 1995;
Nosrat et al., 2001), we
hypothesized that neurotrophins could alter electrophysiological properties of
differentiating ganglion cells. Compared to cultures with BDNF, geniculate neurons with
NGF and NT3 had features of increased excitability including a higher resting membrane
potential and a lower current threshold for the action potential (Al-Hadlaq et al., 2003).
We used TTX to learn about sodium channel properties in different neurotrophin
conditions. In culture with NGF, all E13 trigeminal neurons that were recorded had
TTX-resistant (TTX-R) action potentials (Grigaliunas et al., 2003). In contrast, with BDNF
in culture, action potentials from all recorded neurons were TTX-sensitive (TTX-S). For
the geniculate ganglion, whether in culture with BDNF or NGF, neurons had TTX-S action
potentials.
NGF can up-regulate TTX-R channel transcripts in dorsal root ganglion neurons, and
down-regulate expression of TTX-S channels (Black
et al., 1997). The absence of TTX-S action potentials in our
embryonic trigeminal ganglion neurons sustained with NGF may be attributable to a similar
effect.
In summary, trigeminal and geniculate ganglion neurons, at embryonic stages when the tongue and taste papillae are first innervated, already have distinctive electrophysiological properties including differences in sodium channel expression. These intrinsic properties are susceptible to alteration with molecular exposure, providing an avenue for target organ molecules to regulate innervating neurons.
Supported by NIH, NIDCD Grant DC00456.
|
References |
|---|
|
TopIntroductionPeripheral target organs: tongue...Sensory ganglia: the geniculate...References |
|---|
Al-Hadlaq, S.M., Bradley, R.M., MacCallum, D.K. and Mistretta, C.M. (2003) Embryonic geniculate ganglion neurons in culture have neurotrophin-specific electrophysiological properties. Neuroscience, 118, 145–159.[CrossRef][ISI][Medline]
Black, J.A., Langworthy, K., Hinson, A.W., Dib-Hajj, S.D. and Waxman, S.G. (1997) NGF has opposing effects on Na+ channel III ad SNS gene expression in spinal sensory neurons. Neuroreport, 8, 2331–2335.[ISI][Medline]
Grigaliunas, A., Bradley, R.M., MacCallum, D.K. and Mistretta, C.M. (2002) Distinctive neurophysiological properties of embryonic trigeminal and geniculate neurons in culture. J. Neurophysiol., 88, 2058–2074.
Grigaliunas, A., Mistretta, C., MacCallum, D. and Bradley, R. (2003) Neurotrophins alter sodium channel properties of embryonic trigeminal and geniculate neurons. Association for Chemoreception Sciences, Sarasota, FL.
Ingham, P.W. and McMahon, A.P. (2001) Hedgehog signaling in animal development: paradigms and principles. Genes Dev., 15, 3059–3087.
Liu, H-X. and Mistretta, C.M. (2004) EGF and SHH signals regulating taste papilla pattern in embryonic rat tongue. Program No. 41.1. 2004 Abstract Viewer and Itinerary Planner. Washington, DC: Society for Neuroscience, 2004. Online.
Liu, H-X., MacCallum, D.K., Edwards, C., Gaffield, W. and Mistretta, C.M. (2004) Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development. Dev. Biol., in press.
Mbiene, J-P. and Mistretta, C.M. (1997) Initial innervation of embryonic rat tongue and developing taste papillae: nerves follow distinctive and spatially restricted pathways. Acat. Anat., 160, 139–158.
Mbiene, J-P., MacCallum, D.K. and Mistretta, C.M. (1997) Organ cultures of embryonic rat tongue support tongue and gustatory papilla morphogenesis in vitro without intact sensory ganglia. J. Comp. Neurol., 377, 324–340.[CrossRef][ISI][Medline]
Mistretta, C.M. (1972) Topographical and histological study of the developing rat tongue, palate and taste buds. In Bosma, J.F. (ed.), Oral Sensation and Perception: The Mouth of the Infant. Thomas, Springfield IL, pp. 163–187.
Mistretta, C.M. (1998) The role of innervation in induction and differentiation of taste organs: introduction and background. Ann. N. Y. Acad. Sci., 855, 1–13.
Mistretta, C.M. and Hill, D.L. (2003) Development of the taste system: basic neurobiology. In Doty, R.L. (ed.), Handbook of Olfaction and Gustation, 2nd edn. Marcel Dekker, New York, pp. 759–782.
Mistretta, C.M., Liu, H-X., Gaffield, W. and MacCallum, D.K. (2003) Cyclopamine and jervine in embryonic rat tongue cultures demonstrate a role for Shh signaling in taste papilla development and patterning: fungiform papillae double in number and form in novel locations in dorsal lingual epithelium. Dev. Biol., 254, 1–18.[CrossRef][ISI][Medline]
Nosrat, C.A. and Olson, L. (1995) Brain-derived neurotrophic factor mRNA is expressed in the developing taste bud-bearing tongue papillae of rat. J. Comp. Neurol., 360, 698–704.[CrossRef][ISI][Medline]
Nosrat, C.A., MacCallum, D.K. and Mistretta, C.M. (2001) Distinctive spatiotemporal expression patterns for neurotrophins develop in gustatory papillae and lingual tissues in embryonic tongue organ cultures. Cell Tissue Res., 203, 35–45.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Iwatsuki, H.-X. Liu, A. Gronder, M. A. Singer, T. F. Lane, R. Grosschedl, C. M. Mistretta, and R. F. Margolskee Wnt signaling interacts with Shh to regulate taste papilla development PNAS, February 13, 2007; 104(7): 2253 - 2258. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||