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[P133]: Evolutionary comparison of ER81 regulatory sequences responsible for cerebral‐specific gene expression in mouse and zebrafish
Author(s) -
Langevin L.M.,
Roussigné M.,
Mattar P.,
Scardigli R.,
Logan C.C.,
Blader P.,
Schurrmans C.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.195
Subject(s) - zebrafish , library science , biology , gene , genetics , computer science
The MAP kinases, ERK1 and ERK2, are the central elements of one of the most prominent signaling cascades transducing signals from the cellular environment to cytoplasmic and nuclear effectors. In the brain, the ERKs play critical roles in processes as diverse as neural differentiation, synaptic plasticity and learning. Furthermore, mutations within elements of the MAP Kinase signaling cascade underlie the pathology of numerous genetic developmental disorders, each of which presents with a form of mental retardation. Despite the importance of these proteins, the role of the ERKs in neural development and specifically the consequence of individual ERK1 and ERK2 ablation during early corticogenesis have not been studied. We have therefore examined the function of ERK2 in the developing telencephalon by conditionally inactivating this gene through expression of cre recombinase driven by the glial fibrillary acidic protein (GFAP) promoter. ERK2 is inactivated at embryonic day 13.5 within radial neural progenitor cells, which account for 90% of neurons and glia of the isocortex. The deletion of ERK2 within the GFAP-expressing progenitors results in a substantial reduction in the thickness (20%) of the cerebral cortex. The postnatal brain of ERK2 Conditional Knockout (CKO) mice exhibits fewer neurons within all cortical lamina. Neural progenitor proliferation, evaluated through analysis of mitotic markers and acute BrdU labeling, is dramatically different in the CKO and wildtype brain. The dynamics of cortical neurogenesis are changed such that fewer neurons are born during the peak of neurogenesis. Correspondingly, CKO brains display more progenitor cells residing within the ventricular zone during later developmental periods. This enlarged pool of progenitors subsequently gives rise to an increased number of astrocytes during the gliogenic period, which populate the mature cortex. These data demonstrate that ERK2 specifically acts within the developing telencephalon as a proneural factor by regulating neural progenitor cell proliferation and differentiation.