TY - JOUR
T1 - Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus
AU - Alshammari, Musaad A.
AU - Alshammari, Tahani K.
AU - Nenov, Miroslav N.
AU - Scala, Federico
AU - Laezza, Fernanda
N1 - Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Adult neurogenesis, the production of mature neurons from progenitor cells in the adult mammalian brain, is linked to the etiology of neurodegenerative and psychiatric disorders. However, a thorough understanding of the molecular elements at the base of adult neurogenesis remains elusive. Here, we provide evidence for a previously undescribed function of fibroblast growth factor 14 (FGF14), a brain disease-associated factor that controls neuronal excitability and synaptic plasticity, in regulating adult neurogenesis in the dentate gyrus (DG). We found that FGF14 is dynamically expressed in restricted subtypes of sex determining region Y-box 2 (Sox2)-positive and doublecortin (DCX)-positive neural progenitors in the DG. Bromodeoxyuridine (BrdU) incorporation studies and confocal imaging revealed that genetic deletion of Fgf14 in Fgf14−/− mice leads to a significant change in the proportion of proliferating and immature and mature newly born adult granule cells. This results in an increase in the late immature and early mature population of DCX and calretinin (CR)-positive neurons. Electrophysiological extracellular field recordings showed reduced minimal threshold response and impaired paired-pulse facilitation at the perforant path to DG inputs in Fgf14−/− compared to Fgf14+/+ mice, supporting disrupted synaptic connectivity as a correlative read-out to impaired neurogenesis. These new insights into the biology of FGF14 in neurogenesis shed light into the signaling pathways associated with disrupted functions in complex brain diseases.
AB - Adult neurogenesis, the production of mature neurons from progenitor cells in the adult mammalian brain, is linked to the etiology of neurodegenerative and psychiatric disorders. However, a thorough understanding of the molecular elements at the base of adult neurogenesis remains elusive. Here, we provide evidence for a previously undescribed function of fibroblast growth factor 14 (FGF14), a brain disease-associated factor that controls neuronal excitability and synaptic plasticity, in regulating adult neurogenesis in the dentate gyrus (DG). We found that FGF14 is dynamically expressed in restricted subtypes of sex determining region Y-box 2 (Sox2)-positive and doublecortin (DCX)-positive neural progenitors in the DG. Bromodeoxyuridine (BrdU) incorporation studies and confocal imaging revealed that genetic deletion of Fgf14 in Fgf14−/− mice leads to a significant change in the proportion of proliferating and immature and mature newly born adult granule cells. This results in an increase in the late immature and early mature population of DCX and calretinin (CR)-positive neurons. Electrophysiological extracellular field recordings showed reduced minimal threshold response and impaired paired-pulse facilitation at the perforant path to DG inputs in Fgf14−/− compared to Fgf14+/+ mice, supporting disrupted synaptic connectivity as a correlative read-out to impaired neurogenesis. These new insights into the biology of FGF14 in neurogenesis shed light into the signaling pathways associated with disrupted functions in complex brain diseases.
KW - Adult neurogenesis
KW - Ataxia
KW - Axon initial segment
KW - FGF14
KW - Growth factors
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U2 - 10.1007/s12035-015-9568-5
DO - 10.1007/s12035-015-9568-5
M3 - Article
C2 - 26687232
AN - SCOPUS:84994751896
SN - 0893-7648
VL - 53
SP - 7254
EP - 7270
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 10
ER -