Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex

R. E. Thomson, P. C. Kind, N. A. Graham, M. L. Etherson, J. Kennedy, A. C. Fernandes, C. S. Marques, R. F. Hevner, T. Iwata

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number4
Number of pages16
JournalNeural Development
Volume4
Issue number4
DOIs
Publication statusPublished - Feb 2009

Keywords

  • Prion, Viral, Bacterial and Fungal Pathogens of Animals [LL821]
  • Animal Nutrition (Physiology) [LL510]
  • Non-communicable Diseases and Injuries of Animals [LL860]
  • Animal Physiology and Biochemistry (Excluding Nutrition) [LL600]
  • Animal Surgery and Non-drug Therapy [LL884]
  • bacterial diseases
  • dental caries
  • histology
  • infections
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  • teeth
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  • donkeys
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  • mammals
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  • Chordata
  • animals
  • ungulates
  • eukaryotes
  • asses
  • autopsy
  • bacterial infections
  • bacterioses
  • caries
  • postmortem inspections
  • teeth caries
  • tooth decay

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