FGFR3 regulates brain size by controlling progenitor cell proliferation and apoptosis during embryonic development

Inglis-Broadgate, S. L., Thomson, R. E., Pellicano, F., Tartaglia, M. A., Pontikis, C. C., Cooper, J. D. and Iwata, T. (2005) FGFR3 regulates brain size by controlling progenitor cell proliferation and apoptosis during embryonic development. Developmental Biology, 279(1), pp. 73-85. (doi: 10.1016/j.ydbio.2004.11.035)

Full text not currently available from Enlighten.

Abstract

Mice with the K644E kinase domain mutation in fibroblast growth factor receptor 3 (Fgfr3) (EIIa;Fgfr3+/K644E) exhibited a marked enlargement of the brain. The brain size was increased as early as E11.5, not secondary to the possible effect of Fgfr3 activity in the skeleton. Furthermore, the mutant brains showed a dramatic increase in cortical thickness, a phenotype opposite to that in FGF2 knockout mice. Despite this increased thickness, cortical layer formation was largely unaffected and no cortical folding was observed during embryonic days 11.5–18.5 (E11.5–E18.5). Measurement of cortical thickness revealed an increase of 38.1% in the EIIa;Fgfr3+/K644E mice at E14.5 and the advanced appearance of the cortical plate was frequently observed at this stage. Unbiased stereological analysis revealed that the volume of the ventricular zone (VZ) was increased by more than two fold in the EIIa;Fgfr3+/K644E mutants at E14.5. A relatively mild increase in progenitor cell proliferation and a profound decrease in developmental apoptosis during E11.5–E14.5 most likely accounts for the dramatic increase in total telecephalic cell number. Taken together, our data suggest a novel function of Fgfr3 in controlling the development of the cortex, by regulating proliferation and apoptosis of cortical progenitors.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Dr Rachel and Pellicano, Dr Francesca and Iwata, Dr Tomoko
Authors: Inglis-Broadgate, S. L., Thomson, R. E., Pellicano, F., Tartaglia, M. A., Pontikis, C. C., Cooper, J. D., and Iwata, T.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Developmental Biology
Publisher:Elsevier
ISSN:0012-1606
ISSN (Online):1095-564X
Published Online:08 January 2005

University Staff: Request a correction | Enlighten Editors: Update this record