A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting.
In the mouse, olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) converge their axons to a specific set of glomeruli in the olfactory bulb. To study how OR-instructed axonal fasciculation is controlled, we searched for genes whose expression profiles are correlated with the expressed ORs. Using the transgenic mouse in which the majority of OSNs express a particular OR, we identified such genes coding for the homophilic adhesive molecules Kirrel2/Kirrel3 and repulsive molecules ephrin-A5/EphA5. In the CNGA2 knockout mouse, where the odor-evoked cation influx is disrupted, Kirrel2 and EphA5 were downregulated, while Kirrel3 and ephrin-A5 were upregulated, indicating that these genes are transcribed in an activity-dependent manner. Mosaic analysis demonstrated that gain of function of these genes generates duplicated glomeruli. We propose that a specific set of adhesive/repulsive molecules, whose expression levels are determined by OR molecules, regulate the axonal fasciculation of OSNs during the process of glomerular map formation.
Serizawa
Shou
S
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
Miyamichi
Kazunari
K
Takeuchi
Haruki
H
Yamagishi
Yuya
Y
Suzuki
Misao
M
Sakano
Hitoshi
H
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D036386:Ephrin-A5 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009475:Neurons, Afferent / Q000166:cytology* / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology; D011485:Protein Binding; D036123:Receptor, EphA5 / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D036386:Ephrin-A5; C474214:Kirrel3 protein, mouse; D008565:Membrane Proteins; D018035:Receptors, Odorant; D036123:Receptor, EphA5