Beta1,3-N-acetylglucosaminyltransferase 1 glycosylation is required for axon pathfinding by olfactory sensory neurons
Authors
Henion, Timothy R.Raitcheva, Denitza
Grosholz, Robert
Biellman, Franziska
Skarnes, William C.
Hennet, Thierry
Schwarting, Gerald A.
Document Type
Journal ArticlePublication Date
2005-02-25Keywords
Amino SugarsAnimals
Axons
Carbohydrate Sequence
Cell Death
Enzyme Induction
Feeding Behavior
Ganglia, Spinal
Glycosylation
Mice
Mice, Knockout
Molecular Sequence Data
N-Acetylglucosaminyltransferases
Nerve Degeneration
Nerve Regeneration
Neurons, Afferent
Olfactory Bulb
Polysaccharides
*Protein Processing, Post-Translational
RNA, Messenger
Receptors, Odorant
Synapses
Vomeronasal Organ
Cell Biology
Metadata
Show full item recordAbstract
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.Source
J Neurosci. 2005 Feb 23;25(8):1894-903. Link to article on publisher's siteDOI
10.1523/JNEUROSCI.4654-04.2005Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48914PubMed ID
15728829Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.4654-04.2005