Astrocyte-specific regulation of hMeCP2 expression in Drosophila

• DOI: 10.1242/bio.20149092
• Publication Date: 2014-10-11T04:53:39Z
• Authors: David L. Hess-Hom...; Chia-Yu Fan; Tarun Gupta; Ann-Shyn Chiang; Sarah J. Certel
• Keywords: Expression (computer science)

Alterations in the expression of Methyl-CpG-binding protein 2 (MeCP2) either by mutations or gene duplication leads to a wide spectrum neurodevelopmental disorders including Rett Syndrome and MeCP2 disorder. Common features (RTT), disorder, neuropsychiatric indicate that even moderate changes levels result functional structural cell abnormalities. In this study, we investigated two areas pathophysiology using Drosophila as model system: effects glial gain-of-function activity on circuits controlling sleep behavior, cell-type specific regulation expression. first examined elevated microcircuits expressing human (hMeCP2) astrocytes distinct subsets amine neurons dopamine octopamine (OA) neurons. Depending cell-type, hMeCP2 reduced levels, altered daytime/nighttime patterns, generated maintenance deficits. Second, identified 498 base pair region MeCP2e2 isoform is targeted for astrocytes. Levels full-length hMeCP2e2 mutant RTT R106W decreased temporally spatially regulated manner. contrast, deletion Δ166 was not entire astrocyte population. qPCR experiments revealed reduction transcript suggesting transgenic at transcriptional level. Given phenotypic complexities are caused alterations our results provide insight into cellular mechanisms control link microcircuit abnormalities with defined behavioral