Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis.
Rett syndrome, a neurodevelopmental disorder hypothesized to be due to defective neuronal maturation, is a result of mutations in the mecp2 gene encoding the transcriptional repressor methyl-CpG binding protein (MeCP2). We utilized the olfactory system, which displays postnatal neurogenesis, as a model to investigate MeCP2 expression during development and after injury. MeCP2 expression increased postnatally, localizing to mature olfactory receptor neurons (ORNs) and sustentacular supporting cells. The timing of MeCP2 expression was defined by using detergent ablation (to remove the ORNs) and unilateral olfactory bulbectomy (to remove the ORN target), both of which increase neurogenesis. MeCP2 expression in the ORNs reached prelesioning levels as cells matured after ablation, whereas expression was not completely restored after bulbectomy, in which functional synaptogenesis cannot occur. Thus, MeCP2 expression correlates with the maturational state of ORNs, and precedes synaptogenesis. Identifying the time window of MeCP2 expression should help further clarify the biological defects in Rett syndrome.
Department of Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Deborah R S
DR
Cohen
Valéry
V
Matarazzo
Amy M
AM
Palmer
Yajun
Y
Tu
Ok-Hee
OH
Jeon
Jonathan
J
Pevsner
Gabriele V
GV
Ronnett
D000818:Animals; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D003463:Cues; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009830:Olfactory Bulb / Q000196:embryology / Q000254:growth & development / Q000601:surgery; D009831:Olfactory Mucosa / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497393:Mecp2 protein, mouse; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D019006:Neural Cell Adhesion Molecules; D012097:Repressor Proteins