During differentiation, neurons progressively restrict their fate repressing the expression of specific genes. Here we describe the involvement in such developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic factor that participates to chromatin folding and transcriptional regulation. We previously reported that, due to transcriptional impairments, the maturation of Mecp2 null neurons is delayed. To evaluate whether this could stem from altered progenitors proliferation and differentiation, we investigated whether lack of Mecp2 affects these features both in vitro and in vivo. We show that in Mecp2 null embryonic cortexes the expression of genes defining the identity of proliferating neuroprogenitors is enriched and that their permanence in the G1 phase is prolonged. Moreover, the number of cells transitioning from a stage of maturation to a more mature one is increased in Mecp2 null embryonic cortices, in line with the central role of G1 for cell identity refinement. We thus suggest that, possibly due to the lack of proper transcriptional control normally exerted by Mecp2, fate refinement is impaired in developing null cells. We propose that the maturation delay affecting the developing Mecp2 null cortex originates, at least in part, from deranged mechanisms of cell fate refinement.
Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During Embryonic Cortical Development / C.G. Clementina, S. Linda, D.S. Marco, R. Riccardo L, P. Davide, M. Pagani, N. Landsberger, F. Bedogni. - In: CEREBRAL CORTEX. - ISSN 1047-3211. - 28:5(2018 May), pp. 1846-1856.
|Titolo:||Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During Embryonic Cortical Development|
LANDSBERGER, NICOLETTA (Penultimo) (Corresponding)
BEDOGNI, FRANCESCO (Corresponding)
|Parole Chiave:||Mecp2; Rett syndrome; cerebral cortex; differentiation; fate commitment|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||mag-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/cercor/bhx360|
|Appare nelle tipologie:||01 - Articolo su periodico|