Mini-Symposium
School of Life Sciences, Peking University
13:00-15:00 PM, 28 July, 2016
Room 311, New Life Science Building, Peking University
13:00-13:40 PM Xian-Jie Yang
Establishing and Repairing the Retinal Neural Network
The neural retina is an integral component of the central nervous system, and receives the majority of sensory inputs for humans. The mature mammalian retinas consist of stereotypical neuronal cell types and organization. The retina has long been established as a useful model to study nervous system development, physiology, disease etiology and therapy. We are interested in understanding mechanisms regulating neuronal cell fate specification and circuitry assembly, and how to utilize known developmental principles to control stem cell-based retinal neuron derivation. In addition, we are investigating intercellular signaling events and cellular responses to growth factors that elicit neuroprotection of damaged neurons in retinal degeneration models.
13:40-14:20 PM Ting Xie
Regulation of Ciliary Body Development and Function by Notch Signaling: Potential Insight into Glaucoma Pathogenesis
The ciliary body (CB) of the mammalian eye is responsible for secreting aqueous humor to maintain intraocular pressure, which is elevated in the eyes of glaucoma patients. It contains a folded two-layered epithelial structure comprised of the non-pigmented inner ciliary epithelium (ICE) and the pigmented outer cililary epithelium (OCE), and the underlying stroma. Although the CB has an important function in the eye, its development remains poorly studied. Recently, we have shown that conditional inactivation of Notch2 signaling pathway in the developing CB abolishes its morphogenesis. Notch2 is expressed in the OCE of the CB, whereas Jag1 is expressed in the ICE. Conditional inactivation of Jag1 or Notch2 in the CB disrupts its morphogenesis, but does not affect CB specification. Notch2 signaling promotes cell proliferation and maintains BMP signaling, both of which have been suggested to be important for CB morphogenesis. Although Notch and BMP signaling pathways are known to cross-talk via the interaction between their downstream transcriptional factors, we show that Notch2 maintains BMP signaling in the OCE by repressing expression of secreted BMP inhibitors, representing a novel regulatory strategy. Consistent with the idea that canonical Notch signaling is mediated through RBPJ-dependent gene regulation, CB-specific Rbpj ablation leads to CB morphogenesis and secretion defects by decreasing cell proliferation and BMP signaling. Unlike Notch2 mutant CBs, Rbpj mutant CBs exhibit the ICE-OCE separation due to the decrease in Nectin1-mediated ICE-OCE adhesion, and also show the decreased secretion of aqueous humor proteins. Surprisingly, Notch2, but not RBPJ, is required in the developing CB to maintain active BMP signaling in the underlying stromal cells. Therefore, we have revealed important roles of Notch-RBPJ in regulating CB development and secretion, and have also uncovered the unexpected RBPJ-independent regulation of BMP signaling by Notch2 as well as Notch2-independent RBPJ functions in the developing CB.
14:20-15:00 PM Chuan He
RNA methylation in gene expression regulation
Over 100 types of post-transcriptional RNA modifications have been identified in all kingdoms of life. Prior to our work, no example of reversible chemical modifications on RNA that could affect gene expression had been shown. We have discovered the first two RNA demethylases: FTO, a protein associated with human fat mass obesity and development, and ALKBH5, a protein that affects spermatogenesis in a mouse model. These two proteins catalyze oxidative demethylation of the most prevalent internal modifications of mammalian messenger RNA (mRNA) and other nuclear RNA, N6-methyladenosine (m6A). These findings indicate that reversible RNA modification could impact biological regulation analogous to the well-known reversible DNA and histone chemical modifications. We have also identified and characterized proteins that selectively recognize m6A-modified mRNA and affect the translation status and lifetime of the target mRNA, as well as molecular machines that deposit the m6A methylation on mRNA. Our discoveries reveal a new mode of post-transcriptional gene expression regulation that depends on dynamic/reversible RNA modifications.
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