Dr. Fengwei Yu received his Ph.D. degree at Institute of Molecular and Cell Biology (IMCB), Singapore in 2003. Immediately after that, he joined TLL to establish his independent research group. He was awarded the National Young Scientist Award as the sole winner in the biomedical category for his breakthrough research on neural development and neurological disorders in 2007. He is also an adjunct Associate Professor in Department of Biological Sciences (DBS/NUS), a supervisor in NUS Graduate School for Integrative Sciences and Engineering (NGS/NUS), and Singapore Graduate Programme in Neuroscience (SGPN).
They are interested in understanding developmental, cellular and molecular mechanisms of neuronal pruning and remodeling using a powerful model organism, Drosophila melanogaster or Fruit Fly. A dramatic decrease in neuronal connections, known as neuronal pruning, occurs in adolescent human brains, in response to a robust increase in levels of steroid hormones such as thyroid and sex hormones. Perturbation of the neuronal network maturation may cause some psychiatric disorders, for example, schizophrenia, a disorder associated with excessive pruning occurring in the brain cortex. Hence, adolescence, a transition stage between childhood and adulthood, is the peak age of onset for human psychiatric disorders, during which remarkable physical and behavioral changes take place.
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. They 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. Their 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, Dr. Yu's group 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.
