报告题目： Sculpting the Nervous System: Molecular Mechanisms of Neuronal Pruning in Drosophila

报告人：  Fengwei Yu, Ph.D.

                Principal Investigator, Temasek Life Sciences Laboratory , Singapore

                Department of Biological Sciences, National University of Singapore

主持人： 佟 超   教 授 

时   间：  2011年10月13日（星期四）下午四点  

地   点：  医学院综合楼205报告厅
  

Abstract：

Pruning that selectively removes exuberant or inaccurate axons/dendrites is crucial for sculpting neural circuits during animal development. During Drosophila metamorphosis, dendritic arborization sensory neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone. We previously identified a genetic pathway composed of a critical transcription factor Sox14 and a cytoskeletal regulator Mical that acts downstream of ecdysone receptor (EcR-B1) to govern dendrite pruning in ddaC neurons (Kirilly D., et al., Nature Neuroscience 2009). However, it is unknown whether epigenetic factors are involved in dendrite pruning. Here, we analyzed 81 epigenetic factors, from which a Brahma (Brm)-containing chromatin remodeler and a histone acetyltransferase CREB-binding protein (CBP) were identified for their critical roles in initiating dendrite pruning. Brm and CBP specifically activate a key ecdysone response gene sox14 but not EcR-B1. Furthermore, the HAT activity of CBP is important for sox14 expression and dendrite pruning. Our biochemical assays indicate that EcR-B1 associates with CBP in the presence of ecdysone and facilitates the local enrichment of an active chromatin mark H3K27Ac at the sox14 gene region. Thus, our data, for the first time, reveal that specific intrinsic epigenetic factors cooperate with systemic steroid hormones to activate selective transcriptional programs, thereby initiating remodelling of the nervous system during animal development.

Selected Papers:

Kirilly D., Lim KHE., Wang C., Wong JLJ., Zhang H., Wang H., Wang H. and Yu F*. Intrinsic epigenetic factors cooperate with the steroid hormone ecdysone to govern dendrite pruning in Drosophila. Neuron, in press. 

Kirilly D., Gu Y., Huang Y., Wu Z., Bashirullah A., Low BC, Kolodkin A.L., Wang H. and Yu F*. A genetic pathway comprised of Sox14 and Mical governs severing of dendrites during pruning. Nature Neuroscience, 12, 1497–1505 (2009). [Featured by “News and Views” in Nature Neuroscience 12: 1479-1480 (2009)].