Lactosamine modulates the rate of migration of GnRH neurons during mouse development.
Gonadotropin-releasing hormone (GnRH) neurons are derived from progenitor cells in the olfactory placodes and migrate from the vomeronasal organ (VNO) across the cribriform plate into the forebrain. At embryonic day (E)12 in the mouse most of these neurons are still in the nasal compartment but by E15 most GnRH neurons have migrated into the forebrain. Glycoconjugates with carbohydrate chains containing terminal lactosamine are expressed by neurons in the main olfactory epithelium and in the VNO. One of the key enzymes required to regulate the synthesis and expression of lactosamine, beta1,3-N-acetylglucosaminyltransferase-1 (beta3GnT1), is strongly expressed by neurons in the olfactory epithelium and VNO, and on neurons migrating out of the VNO along the GnRH migratory pathway. Immunocytochemical analysis of lactosamine and GnRH in embryonic mice reveals that the percentage of lactosamine+-GnRH+ double-labeled neurons decreases from > 80% at E13, when migration is near its peak, to approximately 30% at E18.5, when most neurons have stopped migrating. In beta3GnT1-/- mice, there is a partial loss of lactosamine expression on GnRH neurons. Additionally, a greater number of GnRH neurons were retained in the nasal compartment of null mice at E15 while fewer GnRH neurons were detected later in embryonic development in the ventral forebrain. These results suggest that the loss of lactosamine on a subset of GnRH neurons impeded the rate of migration from the nose to the brain.
Bless
Elizabeth
E
Curis Inc., Cambridge, MA 02138, USA.
Raitcheva
Denitza
D
Henion
Timothy R
TR
Tobet
Stuart
S
Schwarting
Gerald A
GA
D000606:Amino Sugars / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019147:Vomeronasal Organ / Q000166:cytology / Q000196:embryology* / Q000378:metabolism
D000606:Amino Sugars; C032233:lactosamine; D007987:Gonadotropin-Releasing Hormone; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases