FGF-dependent, context-driven role for FRS adapters in the early telencephalon

Sayan Nandi, Grigoriy Gutin, Christopher A. Blackwood, Nachiket G. Kamatkar, Kyung W. Lee, Gordon Fishell, Fen Wang, Mitchell Goldfarb, Jean M. Hébert

Research output: Contribution to journalArticle

Abstract

FGF signaling, an important component of intercellular communication, is required in many tissues throughout development to promote diverse cellular processes. Whether FGF receptors (FGFRs) accomplish such varied tasks in part by activating different intracellular transducers in different contexts remains unclear. Here, we used the developing mouse telencephalon as an example to study the role of the FRS adapters FRS2 and FRS3 in mediating the functions of FGFRs. Using tissue-specific and germline mutants, we examined the requirement of Frs genes in two FGFR-dependent processes. We found that Frs2 and Frs3 are together required for the differentiation of a subset of medial ganglionic eminence (MGE)-derived neurons, but are dispensable for the survival of early telencephalic precursor cells, in which any one of three FGFRs (FGFR1, FGFR2, or FGFR3) is sufficient for survival. Although FRS adapters are dispensable for ERK-1/2 activation, they are required for AKT activation within the subventricular zone of the developing MGE. Using an FRS2,3-binding site mutant of Fgfr1, we established that FRS adapters are necessary for mediating most or all FGFR1 signaling, not only in MGE differentiation, but also in cell survival, implying that other adapters mediate at least in part the signaling from FGFR2 and FGFR3. Our study provides an example of a contextual role for an intracellular transducer and contributes to our understanding of how FGF signaling plays diverse developmental roles.

Original languageEnglish (US)
Pages (from-to)5690-5698
Number of pages9
JournalJournal of Neuroscience
Volume37
Issue number23
DOIs
StatePublished - Jun 7 2017

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Fibroblast Growth Factor Receptors
Telencephalon
Median Eminence
Transducers
Lateral Ventricles
Cell Survival
Binding Sites
Neurons
Genes

Keywords

  • FRS2
  • FRS3
  • Signal transduction
  • Signaling adapter
  • Telencephalon

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nandi, S., Gutin, G., Blackwood, C. A., Kamatkar, N. G., Lee, K. W., Fishell, G., ... Hébert, J. M. (2017). FGF-dependent, context-driven role for FRS adapters in the early telencephalon. Journal of Neuroscience, 37(23), 5690-5698. https://doi.org/10.1523/JNEUROSCI.2931-16.2017

FGF-dependent, context-driven role for FRS adapters in the early telencephalon. / Nandi, Sayan; Gutin, Grigoriy; Blackwood, Christopher A.; Kamatkar, Nachiket G.; Lee, Kyung W.; Fishell, Gordon; Wang, Fen; Goldfarb, Mitchell; Hébert, Jean M.

In: Journal of Neuroscience, Vol. 37, No. 23, 07.06.2017, p. 5690-5698.

Research output: Contribution to journalArticle

Nandi, S, Gutin, G, Blackwood, CA, Kamatkar, NG, Lee, KW, Fishell, G, Wang, F, Goldfarb, M & Hébert, JM 2017, 'FGF-dependent, context-driven role for FRS adapters in the early telencephalon', Journal of Neuroscience, vol. 37, no. 23, pp. 5690-5698. https://doi.org/10.1523/JNEUROSCI.2931-16.2017
Nandi, Sayan ; Gutin, Grigoriy ; Blackwood, Christopher A. ; Kamatkar, Nachiket G. ; Lee, Kyung W. ; Fishell, Gordon ; Wang, Fen ; Goldfarb, Mitchell ; Hébert, Jean M. / FGF-dependent, context-driven role for FRS adapters in the early telencephalon. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 23. pp. 5690-5698.
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