Beta1,3-N-acetylglucosaminyltransferase 1 glycosylation is required for axon pathfinding by olfactory sensory neurons.
During embryonic development, axons from sensory neurons in the olfactory epithelium (OE) extend into the olfactory bulb (OB) where they synapse with projection neurons and form glomerular structures. To determine whether glycans play a role in these processes, we analyzed mice deficient for the glycosyltransferase beta1,3-N-acetylglucosaminyltransferase 1 (beta3GnT1), a key enzyme in lactosamine glycan synthesis. Terminal lactosamine expression, as shown by immunoreactivity with the monoclonal antibody 1B2, is dramatically reduced in the neonatal null OE. Postnatal beta3GnT1-/- mice exhibit severely disorganized OB innervation and defective glomerular formation. Beginning in embryonic development, specific subsets of odorant receptor-expressing neurons are progressively lost from the OE of null mice, which exhibit a postnatal smell perception deficit. Axon guidance errors and increased neuronal cell death result in an absence of P2, I7, and M72 glomeruli, indicating a reduction in the repertoire of odorant receptor-specific glomeruli. By approximately 2 weeks of age, lactosamine is unexpectedly reexpressed in sensory neurons of null mice through a secondary pathway, which is accompanied by the regrowth of axons into the OB glomerular layer and the return of smell perception. Thus, both neonatal OE degeneration and the postnatal regeneration are lactosamine dependent. Lactosamine expression in beta3GnT1-/- mice is also reduced in pheromone-receptive vomeronasal neurons and dorsal root ganglion cells, suggesting that beta3GnT1 may perform a conserved function in multiple sensory systems. These results reveal an essential role for lactosamine in sensory axon pathfinding and in the formation of OB synaptic connections.
Henion
Timothy R
TR
Shriver Center, Waltham, Massachusetts 02452, USA.
Raitcheva
Denitza
D
Grosholz
Robert
R
Biellmann
Franziska
F
Skarnes
William C
WC
Hennet
Thierry
T
Schwarting
Gerald A
GA
D000606:Amino Sugars / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D002240:Carbohydrate Sequence; D016923:Cell Death; D004790:Enzyme Induction; D005247:Feeding Behavior; D005727:Ganglia, Spinal / Q000166:cytology; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009410:Nerve Degeneration; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D009830:Olfactory Bulb / Q000166:cytology* / Q000201:enzymology / Q000473:pathology; D011134:Polysaccharides / Q000096:biosynthesis / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D018035:Receptors, Odorant / Q000502:physiology; D013569:Synapses / Q000502:physiology; D019147:Vomeronasal Organ / Q000166:cytology
D000606:Amino Sugars; D011134:Polysaccharides; D012333:RNA, Messenger; D018035:Receptors, Odorant; C032233:lactosamine; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases
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