Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons.

By Richard D. Smrt, Julialea Eaves-Egenes, B. Barkho, Nicholas J. Santistevan, Chunmei Zhao, James Bradley Aimone, Fred H. Gage, Xinyu Zhao. 2007

255 citations recorded by the source corpus.

It is well known that Rett Syndrome, a severe postnatal childhood neurological disorder, is mostly caused by mutations in the MECP2 gene. However, how deficiencies in MeCP2 contribute to the neurological dysfunction of Rett Syndrome is not clear. We aimed to resolve the role of MeCP2 epigenetic regulation in postnatal brain development in an Mecp2-deficient mouse model. We found that, while Mecp2 was not critical for the production of immature neurons in the dentate gyrus (DG) of the hippocampus, the newly generated neurons exhibited pronounced deficits in neuronal maturation, including delayed transition into a more mature stage, altered expression of presynaptic proteins and reduced dendritic spine density. Furthermore, analysis of gene expression profiles of isolated DG granule neurons revealed abnormal expression levels of a number of genes previously shown to be important for synaptogenesis. Our studies suggest that MeCP2 plays a central role in neuronal maturation, which might be mediated through epigenetic control of expression pathways that are instrumental in both dendritic development and synaptogenesis.

Subfields: Genetics, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. Peng Jin
5. Xinyu Zhao
6. Keith E. Szulwach
7. German Ignacio Parisi

In Molecular Biology

1. Hongjun Song
2. Guo-li Ming
3. Fred H. Gage
4. Peng Jin
5. Jiawei Sun
6. Jiaqi Sun
7. Xinyu Zhao
8. Keith E. Szulwach

Citations in the corpus

• Epigenetic regulation of neurogenesis in the adult mammalian brain (2011, background): “In the adult dentate gyrus of MeCP2-knockout mice, newborn neurons exhibit pronounced deficits in their neuronal maturation and spine formation (Smrt et al., 2007), suggesting a conserved function of”
• The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”
• Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, methodology): “These analyses were carried out using our established method [32,34].”
• Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation (2010, unknown): “To assess gene functions in adult neurogenesis, we and others have used recombinant retroviruses that are only capable of infecting dividing cells to selectively transduce single dispersed aNSCs in the adult hippocampus (Ge et al., 2006; Smrt et al., 2007; van Praag et al., 2002).”