Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse.
Fibroblast growth factor receptor 1 (Fgfr1) is expressed at high levels by progenitor cells of the ventricular zone (VZ) within the hippocampal primordium. To investigate the role of Fgfr1 in these cells, in vivo Cre recombination of "floxed" Fgfr1 alleles was directed to cells of the radial glial lineage by using the human glial fibrillary acidic protein promoter. Radial glial-like cells of the hippocampal VZ are the progenitors of pyramidal neurons and granule cells of hippocampal dentate gyrus (DG). Mice carrying null Fgfr1 alleles (Fgfr1(Deltaflox)) in cells of this lineage showed a dramatic loss of Fgfr1 gene expression throughout the embryonic dorsal telencephalon. These Fgfr1(Deltaflox) mice exhibited a approximately 30% decrease in dividing radial glial progenitor cells in the hippocampal VZ and DG in the late embryonic period, progressing to a approximately 50-60% loss at birth, without any changes in cell survival. In addition, no FGF2-sensitive neural stem cells could be isolated from the Fgfr1(Deltaflox) hippocampal neuroepithelium, whereas epidermal growth factor-sensitive neural stem cells were not affected. The number of hippocampal pyramidal neurons and DG granule cells was approximately 30-50% decreased from the perinatal period through adulthood, and the number of parvalbumin-containing interneurons was similarly decreased in both the DG and pyramidal cell fields. We conclude that Fgfr1 is necessary for hippocampal growth, because it promotes the proliferation of hippocampal progenitors and stem cells during development.
Ohkubo
Yasushi
Y
Child Study Center, Yale University, New Haven, Connecticut 06520, USA.
Uchida
Ayumi O
AO
Shin
Dana
D
Partanen
Juha
J
Vaccarino
Flora M
FM
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002452:Cell Count; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020271:Heredodegenerative Disorders, Nervous System / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development* / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D020547:Lateral Ventricles / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D017966:Pyramidal Cells / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019076:Transgenes
D000943:Antigens, Differentiation; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1