title: Fibroblast Growth Factor 14 Modulates the Neurogenesis of Granule Neurons in the Adult Dentate Gyrus.
abstract: 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.
authors.affiliation: Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX, USA.|Graduate Studies Abroad Program, King Saud University, Riyadh, Saudi Arabia.|Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Medical Research Building 7.102B, 301 University Boulevard, Galveston, TX, 77555, USA.
authors.forename: Musaad A
authors.initials: MA
authors.lastname: Alshammari
authors.affiliation: Pharmacology and Toxicology Graduate Program, The University of Texas Medical Branch, Galveston, TX, USA.|Graduate Studies Abroad Program, King Saud University, Riyadh, Saudi Arabia.|Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Medical Research Building 7.102B, 301 University Boulevard, Galveston, TX, 77555, USA.
authors.forename: Tahani K
authors.initials: TK
authors.lastname: Alshammari
authors.affiliation: Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Medical Research Building 7.102B, 301 University Boulevard, Galveston, TX, 77555, USA.
authors.forename: Miroslav N
authors.initials: MN
authors.lastname: Nenov
authors.affiliation: Biophysics Graduate Program, Institute of Human Physiology, Università Cattolica, Rome, Italy.|Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Medical Research Building 7.102B, 301 University Boulevard, Galveston, TX, 77555, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Scala
authors.affiliation: Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch, Galveston, TX, USA. felaezza@utmb.edu.|Center for Addiction Research, The University of Texas Medical Branch, Galveston, TX, USA. felaezza@utmb.edu.|Center for Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX, USA. felaezza@utmb.edu.|Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Medical Research Building 7.102B, 301 University Boulevard, Galveston, TX, 77555, USA. felaezza@utmb.edu.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Laezza
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002452:Cell Count; D002454:Cell Differentiation; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008297:Male; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors
keywords: Adult neurogenesis; Ataxia; Axon initial segment; FGF14; Growth factors