Investigations of the methyl CpG binding domain-containing factor MBD3 in neuronal development and neuronal differentiation.
Published: 2005
Language: eng
Number of pages: 270
Description: Second, the effect of brain challenges on the expression of MBD-containing factors was investigated. Hippocampal expression of MBD-containing factors was examined in two different models of brain challenge: global ischemia and electrical kindling. Each challenge led to significant but differential alterations in mRNA expression of the individual family members. The expression of MBD3 after each respective challenge was found to be unique. Unlike the expression of MeCP2, MBD1, and MBD2, which were induced following these challenges, the expression of MBD3 was diminished following global ischemia but induced following kindling.Taken together, these findings demonstrate MBD3 to be an atypical MBD-containing family member.Methyl CpG binding domain-containing (MBD) factors participate in the epigenetic regulation of gene expression. This thesis describes the characterization of MBD3 and other MBD-containing family members in the developing rat brain. It further describes investigations into the role of MBD3 in neuronal differentiation.Finally, it was found that MBD3 expression decreases as NG108-15 cells differentiate, whereas MeCP2 expression increases. Transient over-expression of MBD3 in cultured primary cortical neurons failed to affect their viability or morphological complexity. In contrast, MeCP2 over-expression increased the morphological complexity of these neurons.First, MBD3 expression was examined in the developing brain. In the embryonic and perinatal brain, MBD3 exhibits a restricted pattern of expression, being pronounced in the forebrain, and less pronounced in mid- and hindbrain regions. In the adult brain, MBD3 expression is prominent in the cortex, hippocampus and cerebellum, and overlaps with neurogenic regions. The prevalence of MBD3 declines from embryonic levels in both the hippocampus and cortex as these tissues mature. The expression profile for MBD3 in the developing brain contrasts with the spatial and temporal expression of the other MBD-containing family members. In contrast to MBD3, MeCP2 is expressed throughout the developing brain, whereas MBD2 displays minimal expression in the developing brain.Third, the regulation of the MBD3 gene was investigated by studying a &sim;1 kilobase genomic sequence upstream of exon 1. A minimal promoter was found to reside within this sequence that was capable of driving transgene expression in primary neurons and in a transgenic mouse.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5253.

Thesis (Ph.D.)--University of Toronto, 2005.

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