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[P1.38]: Effect of hyperoxia treatment on aquaporin 4 changes and edema formation in the contralateral brain after neonatal hypoxia/ischemia
Author(s) -
Ferrari D.C.,
NesicTaylor O.,
PerezPolo J.R.
Publication year - 2008
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.2008.09.088
Subject(s) - hypoxia (environmental) , hyperoxia , brain edema , medicine , humanities , art , chemistry , oxygen , lung , organic chemistry
interactions directing this mode of migration we carried out a forward genetic screen to identify mutations that disrupt the development of ventral telencephalic derivatives and tangential migration in the mouse. Four lines obtained show defects in the migration of GABA-ergic interneurons. In one of these the causative mutation was found in the gene encoding the forkhead transcription factor Foxc1. This novel allele (Foxc1) represents a hypomorph resulting from a destabilized protein. While heterozygote animals do not show any defects in interneuron distribution or general development, homozygous mutants, which survive to adulthood, display a wide array of phenotypic alterations in brain and skull morphology, including amild hydrocephalus and cortical lamination defects attributed to defective meningeal signaling. Developmentally, we observed that Foxc1 mice have a dramatic disorganization of interneuron distribution at the peak of tangential migration (E14.5 to E18.5), especially in the most dorsomedial regions of the cortex. Interestingly, the disorganization of interneuronmigration predominantly affects the superficial migratory stream, resting in the marginal zone, leaving the deeper migratory stream in the intermediate zone relatively unaffected. This suggested a defect in interneuron association with the meninges, thus we examined the expression of a regulator of tangential migration known to be expressed by the meninges and regulating neuronal positioning in the marginal zone, the chemokine CXCL12. We found that CXCL12 expression in the marginal zone and overlying leptomeninges is severely reduced in Foxc1 mice implying that Foxc1 plays a critical role in meningeal development including regulation of the expression of meningeally produced chemotactic ligands.