1. Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex
- Author
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Nicholas Graham, Michelle L Etherson, John W. Kennedy, Robert F. Hevner, Ana Fátima Carvalho Fernandes, Peter C. Kind, Catia S Marques, Rachel E. Thomson, and Tomoko Iwata
- Subjects
Cellular differentiation ,Fibroblast growth factor ,lcsh:RC346-429 ,tooth decay ,necrosis ,Mice ,ungulates ,infections ,Chordata ,In Situ Hybridization ,Mice, Knockout ,Neurons ,bacterial diseases ,pathogenesis ,donkeys ,Neurogenesis ,Cell Cycle ,Cell Differentiation ,Animal Surgery and Non-drug Therapy [LL884] ,ultrastructure ,Immunohistochemistry ,Temporal Lobe ,animals ,medicine.anatomical_structure ,Cerebral cortex ,postmortem inspections ,Occipital Lobe ,Signal transduction ,Research Article ,Signal Transduction ,postmortem examinations ,tomography ,Biology ,histology ,eukaryotes ,autopsy ,FGF8 ,Prosencephalon ,Animal Nutrition (Physiology) [LL510] ,Developmental Neuroscience ,Non-communicable Diseases and Injuries of Animals [LL860] ,medicine ,Animals ,Receptor, Fibroblast Growth Factor, Type 3 ,mammals ,lcsh:Neurology. Diseases of the nervous system ,Perissodactyla ,teeth ,caries ,teeth caries ,FGF15 ,Equidae ,Animal Physiology and Biochemistry (Excluding Nutrition) [LL600] ,Mice, Inbred C57BL ,Equus ,bacterial infections ,Mutation ,dental caries ,Prion, Viral, Bacterial and Fungal Pathogens of Animals [LL821] ,pathology ,bacterioses ,vertebrates ,asses ,Neuroscience ,Developmental biology - Abstract
Background Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown. Results In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis. Conclusion Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex.
- Published
- 2009
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