Role of IGF signaling in olfactory sensory map formation and axon guidance.
Olfactory neurons project their axons to spatially invariant glomeruli in the olfactory bulb, forming an ordered pattern of innervation comprising the olfactory sensory map. A mirror symmetry exists within this map, such that neurons expressing a given receptor typically project to one glomerulus on the medial face and one glomerulus on the lateral face of the bulb. The mechanisms underlying an olfactory neuron's choice to project medially versus laterally remain largely unknown, however. Here we demonstrate that insulin-like growth factor (IGF) signaling is required for sensory innervation of the lateral olfactory bulb. Mutations that eliminate IGF signaling cause axons destined for targets in the lateral bulb to shift to ectopic sites on the ventral-medial surface. Using primary cultures of olfactory and cerebellar neurons, we further show that IGF is a chemoattractant for axon growth cones. Together these observations reveal a role of IGF signaling in sensory map formation and axon guidance.
Scolnick
Jonathan A
JA
Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Functional Genomics Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA.
Cui
Kai
K
Duggan
Cynthia D
CD
Xuan
Shouhong
S
Yuan
Xiao-Bing
XB
Efstratiadis
Argiris
A
Ngai
John
J
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology; D002630:Chemotactic Factors / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D051842:Olfactory Marker Protein / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000196:embryology / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D002630:Chemotactic Factors; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D051842:Olfactory Marker Protein; C519530:insulin-like growth factor-1, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II