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Publication : Cell-autonomous role of GFRα1 in the development of olfactory bulb GABAergic interneurons.

First Author  Zechel S Year  2018
Journal  Biol Open Volume  7
Issue  5 PubMed ID  29716946
Mgi Jnum  J:262197 Mgi Id  MGI:6159442
Doi  10.1242/bio.033753 Citation  Zechel S, et al. (2018) Cell-autonomous role of GFRalpha1 in the development of olfactory bulb GABAergic interneurons. Biol Open 7(5):bio033753
abstractText  GFRalpha1, a receptor for glial cell line-derived neurotrophic factor (GDNF), is critical for the development of the main olfactory system. The olfactory bulb (OB) of Gfra1 knockout mice shows significant reductions in the number of olfactory sensory neurons, mitral and tufted cells, as well as all major classes of OB GABAergic interneurons. However, the latter do not express significant levels of GFRalpha1, leaving the mechanism of action of GFRalpha1 in OB interneuron development unexplained. Here we report that GFRalpha1 is highly expressed in the precursor cells that give rise to all major classes of OB interneurons, but is downregulated as these neurons mature. Conditional ablation of GFRalpha1 in embryonic GABAergic cells recapitulated the cell losses observed in global Gfra1 knockouts at birth. GFRalpha1 was also required for the sustained generation and allocation of OB interneurons in adulthood. Conditional loss of GFRalpha1 altered the migratory behaviour of neuroblasts along the rostral migratory stream (RMS) as well as RMS glial tunnel formation. Together, these data indicate that GFRalpha1 functions cell-autonomously in subpopulations of OB interneuron precursors to regulate their generation and allocation in the mammalian OB.
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