FGFR Regulation of Dendrite Elaboration in Adult-born Granule Cells Depends on Intracellular Mediator and Proximity to the Soma

Marta Grońska-Pęski, Wenzhu Mowrey, Jean M. Hébert

Research output: Contribution to journalArticlepeer-review

Abstract

Fibroblast Growth Factor Receptors (FGFRs) play crucial roles in promoting dendrite growth and branching during development. In mice, three FGFR genes, Fgfr1, Fgfr2, and Fgfr3, remain expressed in the adult neurogenic niche of the hippocampal dentate gyrus. However, the function of FGFRs in the dendritic maturation of adult-born neurons remains largely unexplored. Here, using conditional alleles of Fgfr1, Fgfr2, and Fgfr3 as well as Fgfr1 alleles lacking binding sites for Phospholipase-Cγ (PLCγ) and FGF Receptor Substrate (FRS) proteins, we test the requirement for FGFRs in dendritogenesis of adult-born granule cells. We find that deleting all three receptors results in a small decrease in proximal dendrite elaboration. In contrast, specifically mutating Tyr766 in FGFR1 (a PLCγ binding site) in an Fgfr2;Fgfr3 deficient background results in a dramatic increase of overall dendrite elaboration, while blocking FGFR1-FRS signaling causes proximal dendrite deficits and, to a lesser extent than Tyr766 mutants, increases distal dendrite elaboration. These findings reveal unexpectedly complex roles for FGFRs and their intracellular mediators in regulating proximal and distal dendrite elaboration, with the most notable role in suppressing distal elaboration through the PLCγbinding site.

Original languageEnglish (US)
Pages (from-to)148-167
Number of pages20
JournalNeuroscience
Volume453
DOIs
StatePublished - Jan 15 2021

Keywords

  • FGFR
  • FRS
  • PLCγ
  • dendritogenesis
  • dentate gyrus

ASJC Scopus subject areas

  • Neuroscience(all)

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