TY - JOUR
T1 - Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis
AU - Cohen, Deborah R.S.
AU - Matarazzo, Valéry
AU - Palmer, Amy M.
AU - Tu, Yajun
AU - Jeon, Ok Hee
AU - Pevsner, Jonathan
AU - Ronnett, Gabriele V.
N1 - Funding Information:
We are especially grateful to Andrea Hanlon and Babar Khokhar for excellent technical assistance. We thank Rivka Rachel for helpful comments and the members of the Ronnett lab for helpful discussions and advice. This study was supported by a grant from the International Rett Syndrome Association (IRSA) and NIH grants from the NINDS and NIDCD to G.V.R., and an F32 Fellowship from the NIDCD to D.R.S.C.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1044-7431(03)00026-5
DO - 10.1016/S1044-7431(03)00026-5
M3 - Article
C2 - 12727440
AN - SCOPUS:0037396585
SN - 1044-7431
VL - 22
SP - 417
EP - 429
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 4
ER -