Increased expression of insulin-like growth factor-I (IGF-I) during embryonic development produces neocortical overgrowth with differentially greater effects on specific cytoarchitectonic areas and cortical layers.
The in vivo actions of insulin-like growth factor-I (IGF-I) on the growth and development of the cerebral cortex were investigated in transgenic (Tg) mice that overexpress IGF-I in the brain, beginning as early as embryonic day (E) 13. Compared to non-Tg littermate controls, Tg mice at postnatal day (P) 12 exhibited significant increases in total cortical volume (31%) and in total neuron number (27%). The numerical density of neurons did not differ significantly between Tg and control mice, except in layer I. Comparing cytoarchitectonic areas in Tg mice, significantly greater increases in cortical volume were found for the motor cortex (42%), compared to somatosensory cortex (35%). Similarly, greater increases in total neuron number were found for motor cortex (44%) compared to somatosensory cortex (28%). Comparing individual cortical layers in Tg mice, the greatest increase in neuron number was found in layer I for both motor (93%) and somatosensory (76%) regions, followed by layer V (36-53%)>II/III (26-47%)>VI (26-37%)>IV (22-34%). Our results demonstrate that increased expression of IGF-I in vivo during embryonic and early postnatal development produces substantial overgrowth of the neocortex. IGF-I-mediated growth and development exhibits differential effects in some cytoarchitectonic areas and in lamina-specific neuron populations, most notably the neurons of layer I.
Hodge
Rebecca D
RD
Department of Pathology and Laboratory Medicine, University of British Columbia, B.C. Research Institute for Children's and Women's Health, 950 West 28th Avenue, Vancouver, British Columbia, Canada, V5Z 4H4.
D'Ercole
A Joseph
AJ
O'Kusky
John R
JR
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000502:physiology*
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D007334:Insulin-Like Growth Factor I