Abstract |
The immunoglobulin superfamily member TAG-1 plays an important role in neurite outgrowth, fasciculation, neuronal migration and axon guidance during development. The main projection neurons of the olfactory bulb (mitral and tufted cells) express TAG-1 during development but the exact role of this molecule in the olfactory system has not yet been investigated. The aim of the present project is to study the organization and development of the olfactory system in mice deficient for TAG-1 (Tag-1-/-).
Using immunohistochemistry against mitral-cell markers on cryosections of adult olfactory bulb (OB) from mutant and control mice, we observed significantly decreased numbers of mitral cells in Tag-1-/- mice when compared with wild type animals. Furthermore, this defect in mitral cells number was already evident at the day of birth (P0) in the OB of Tag-1-/- mice. These results suggest that the defect in mitral cells number can be attributed to deficits during the development of the olfactory bulb, either affecting apoptosis or cell proliferation. Immunohistochemical experiments in OB cryosections at various developmental stages revealed no difference in cell apoptosis. In order to study the proliferation capacity of the mitral cells population, we administrated 5’-bromo 2-deoxyuridine (BrdU) at embryonic day 11.5 (E11.5, generation of the majority of mitral cells) and sacrificed the embryos at E18.5 (mature OB). In cryosections from the above animals we detected a decrease in BrdU+ cells found in mitral cell layer (MCL) of Tag-1-/- compared to wild type. The above data suggest that lack of TAG-1 leads to defects during development of the olfactory system that could result either from proliferation deficits of mitral cells progenitors nor from misguidance defects. We are currently investigating these possibilities.
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