Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis

Sayan Nandi, Karina Alviña, Pablo J. Lituma, Pablo E. Castillo, Jean M. Hebert

Research output: Contribution to journalArticle

Abstract

Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development.

Original languageEnglish (US)
Pages (from-to)192-201
Number of pages10
JournalNeuroscience
Volume369
DOIs
StatePublished - Jan 15 2018

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Nerve Growth Factors
Fibroblast Growth Factor Receptors
Proteins
Dendritic Spines
Neurogenesis
Dentate Gyrus
Brain
Morphogenesis
Photons
Hippocampus
Intercellular Signaling Peptides and Proteins

Keywords

  • FGF
  • FRS
  • hippocampus
  • neurogenesis
  • neurotrophin
  • synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis",
abstract = "Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development.",
keywords = "FGF, FRS, hippocampus, neurogenesis, neurotrophin, synaptogenesis",
author = "Sayan Nandi and Karina Alvi{\~n}a and Lituma, {Pablo J.} and Castillo, {Pablo E.} and Hebert, {Jean M.}",
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T1 - Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis

AU - Nandi, Sayan

AU - Alviña, Karina

AU - Lituma, Pablo J.

AU - Castillo, Pablo E.

AU - Hebert, Jean M.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development.

AB - Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development.

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