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


CONCLUSIONS
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.
Thomson
Rachel E
RE
Division of Cancer Sciences and Molecular Pathology, University of Glasgow, Beatson Laboratories for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. rachel.thomson@florey.edu.au
Kind
Peter C
PC
Graham
Nicholas A
NA
Etherson
Michelle L
ML
Kennedy
John
J
Fernandes
Ana C
AC
Marques
Catia S
CS
Hevner
Robert F
RF
Iwata
Tomoko
T
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009778:Occipital Lobe / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013702:Temporal Lobe / Q000378:metabolism*
C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3