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Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification.

Publication ,  Journal Article
Donnelly, CR; Shah, AA; Mistretta, CM; Bradley, RM; Pierchala, BA
Published in: Proc Natl Acad Sci U S A
January 16, 2018

The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversification of chemosensory neurons within the geniculate ganglion (GG). GDNF, acting through the receptor tyrosine kinase Ret, regulates the expression of the chemosensory fate determinant Phox2b early in GG development. Ret-/- mice, but not Retfx/fx ; Phox2b-Cre mice, display a profound loss of Phox2b expression with subsequent chemosensory innervation deficits, indicating that Ret is required for the initial amplification of Phox2b expression but not its maintenance. Ret expression is extinguished perinatally but reemerges postnatally in a subpopulation of large-diameter GG neurons expressing the mechanoreceptor marker NF200 and the GDNF coreceptor GFRα1. Intriguingly, we observed that ablation of these neurons in adult Ret-Cre/ERT2; Rosa26LSL-DTA mice caused a specific loss of tactile, but not chemical or thermal, electrophysiological responses. Overall, the GDNF-Ret pathway exerts two critical and distinct functions in the peripheral taste system: embryonic chemosensory cell fate determination and the specification of lingual mechanoreceptors.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 16, 2018

Volume

115

Issue

3

Start / End Page

E516 / E525

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor Brn-3A
  • Touch
  • Tongue
  • Temperature
  • Taste
  • Tamoxifen
  • Signal Transduction
  • RNA, Untranslated
  • Pyrimidines
 

Citation

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Donnelly, C. R., Shah, A. A., Mistretta, C. M., Bradley, R. M., & Pierchala, B. A. (2018). Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification. Proc Natl Acad Sci U S A, 115(3), E516–E525. https://doi.org/10.1073/pnas.1708838115
Donnelly, Christopher R., Amol A. Shah, Charlotte M. Mistretta, Robert M. Bradley, and Brian A. Pierchala. “Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification.Proc Natl Acad Sci U S A 115, no. 3 (January 16, 2018): E516–25. https://doi.org/10.1073/pnas.1708838115.
Donnelly CR, Shah AA, Mistretta CM, Bradley RM, Pierchala BA. Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification. Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E516–25.
Donnelly, Christopher R., et al. “Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification.Proc Natl Acad Sci U S A, vol. 115, no. 3, Jan. 2018, pp. E516–25. Pubmed, doi:10.1073/pnas.1708838115.
Donnelly CR, Shah AA, Mistretta CM, Bradley RM, Pierchala BA. Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification. Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E516–E525.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

January 16, 2018

Volume

115

Issue

3

Start / End Page

E516 / E525

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor Brn-3A
  • Touch
  • Tongue
  • Temperature
  • Taste
  • Tamoxifen
  • Signal Transduction
  • RNA, Untranslated
  • Pyrimidines