A contextual model for axonal sorting into glomeruli in the mouse olfactory system.
No models fully account for how odorant receptors (ORs) function in the guidance of axons of olfactory sensory neurons (OSNs) to glomeruli in the olfactory bulb. Here, we use gene targeting in mice to demonstrate that the OR amino acid sequence imparts OSN axons with an identity that allows them to coalesce into glomeruli. Replacements between the coding regions of the M71 and M72 OR genes reroute axons to their respective glomeruli. A series of M71-M72 hybrid ORs uncover a spectrum of glomerular phenotypes, leading to the concept that the identity of OSN axons is revealed depending on what other axons are present. Naturally occurring amino acid polymorphisms in other ORs also produce distinct axonal identities. These critical amino acid residues are distributed throughout the protein and reside predominantly within transmembrane domains. We propose a contextual model for axon guidance in which ORs mediate homotypic interactions between like axons.
Feinstein
Paul
P
The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. feinstp@rockefeller.edu
Mombaerts
Peter
P
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018390:Gene Targeting; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D018035:Receptors, Odorant