Research Awards
Xinyu Zhao, Ph.D.
University of New Mexico
Fred H. Gage, Ph.D.
Salk Institute
"Function of MeCP2 in postnatal neurogenesis and neuroprogenitor cell biology"
2-Year Award - $99,987
Research Sponsor: Anonymous
Final Report (November 2005)
Rett syndrome is primarily caused by mutation of MeCP2, a methyl-CpG binding protein (MBD) that binds to methylated DNA in the genome and facilitates transcriptional repression. Using a mouse knockout model, we analyzed the role of MeCP2 in neurogenesis during postnatal development, a period comparable to the onset of symptoms in human Rett patients. Though we found that MeCP2 was not critical for the generation of new neurons, both in culture and in mammalian brains, MeCP2 mutant mice displayed abnormal presynaptic protein expression and distribution, and had a smaller hippocampus. To determine whether MeCP2 was critical for postnatal neuronal maturation, we grafted GFP-expressing retrovirus into the hippocampus of 4-week-old mice to label dividing neural stem and progenitor cells, and analyzed the new neurons at 4-weeks post-infection. We found that new neurons generated in postnatal MeCP2 mutant mice had reduced dendritic spine densities and increased variations in spine distribution compared to wild type mice, suggesting deficits in neuronal maturation. Our work demonstrates that MeCP2 is not critical for generating new neurons in postnatal brains but may be essential for their maturation. Exploring the role of MeCP2 in the maturation and maintenance of new neurons in postnatal brain is a crucial step towards understanding the etiology of Rett Syndrome.
Xinyu Zhao, Ph.D.University of New Mexico
Fred H. Gage, Ph.D.
Salk Institute
"Function of MeCP2 in postnatal neurogenesis and neuroprogenitor cell biology"
2-Year Award - $99,987Research Sponsor: Anonymous
Final Report (November 2005)
Rett syndrome is primarily caused by mutation of MeCP2, a methyl-CpG binding protein (MBD) that binds to methylated DNA in the genome and facilitates transcriptional repression. Using a mouse knockout model, we analyzed the role of MeCP2 in neurogenesis during postnatal development, a period comparable to the onset of symptoms in human Rett patients. Though we found that MeCP2 was not critical for the generation of new neurons, both in culture and in mammalian brains, MeCP2 mutant mice displayed abnormal presynaptic protein expression and distribution, and had a smaller hippocampus. To determine whether MeCP2 was critical for postnatal neuronal maturation, we grafted GFP-expressing retrovirus into the hippocampus of 4-week-old mice to label dividing neural stem and progenitor cells, and analyzed the new neurons at 4-weeks post-infection. We found that new neurons generated in postnatal MeCP2 mutant mice had reduced dendritic spine densities and increased variations in spine distribution compared to wild type mice, suggesting deficits in neuronal maturation. Our work demonstrates that MeCP2 is not critical for generating new neurons in postnatal brains but may be essential for their maturation. Exploring the role of MeCP2 in the maturation and maintenance of new neurons in postnatal brain is a crucial step towards understanding the etiology of Rett Syndrome.