Person: Shen, Yu Serena
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Yu Serena
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Shen, Yu Serena
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Publication An Insulin-to-Insulin Regulatory Network Orchestrates Phenotypic Specificity in Development and Physiology(Public Library of Science, 2014) Fernandes de Abreu, Diana Andrea; Caballero, Antonio; Fardel, Pascal; Stroustrup, Nicholas Edward; Chen, Zhunan; Lee, KyungHwa; Keyes, William D.; Nash, Zachary M.; López-Moyado, Isaac F.; Vaggi, Federico; Cornils, Astrid; Regenass, Martin; Neagu, Anca; Ostojic, Ivan; Liu, Chang; Cho, Yongmin; Sifoglu, Deniz; Shen, Yu Serena; Fontana, Walter; Lu, Hang; Csikasz-Nagy, Attila; Murphy, Coleen T.; Antebi, Adam; Blanc, Eric; Apfeld, Javier; Zhang, Yun; Alcedo, Joy; Ch'ng, QueeLimInsulin-like peptides (ILPs) play highly conserved roles in development and physiology. Most animal genomes encode multiple ILPs. Here we identify mechanisms for how the forty Caenorhabditis elegans ILPs coordinate diverse processes, including development, reproduction, longevity and several specific stress responses. Our systematic studies identify an ILP-based combinatorial code for these phenotypes characterized by substantial functional specificity and diversity rather than global redundancy. Notably, we show that ILPs regulate each other transcriptionally, uncovering an ILP-to-ILP regulatory network that underlies the combinatorial phenotypic coding by the ILP family. Extensive analyses of genetic interactions among ILPs reveal how their signals are integrated. A combined analysis of these functional and regulatory ILP interactions identifies local genetic circuits that act in parallel and interact by crosstalk, feedback and compensation. This organization provides emergent mechanisms for phenotypic specificity and graded regulation for the combinatorial phenotypic coding we observe. Our findings also provide insights into how large hormonal networks regulate diverse traits.Publication Neural Mechanisms of Gait Regulation and Olfactory Plasticity in Caenorhabditis elegans(2015-01-29) Shen, Yu Serena; Zhang, YunOne of the fundamental questions in biological science is to understand how the nervous system functions to generate behavior. The past decades have witnessed much progress in behavioral neuroscience, but it is often challenging to gain mechanistic insights at the molecular and cellular level. The small nervous system and experimental accessibility of the nematode Caenorhabditis elegans offer an opportunity to study neural mechanisms underlying behavior in greater detail. Because many of the genes and proteins are conserved across species, studies in C. elegans provide useful information to the broad research community. In this dissertation, I use the locomotory gait regulation and olfactory aversive learning as two examples to demonstrate that C. elegans neurobiology can offer unique insights into the organization of behavior in more complex organisms. Chapter 2 of this dissertation characterizes a small neuronal circuit that modulates the amplitude of head deflection in C. elegans. C. elegans moves its head rhythmically along the dorsal-ventral axis during forward movement. By quantifying local head curvature, I found the cholinergic SMD neurons facilitate head deflection, whereas the GABAergic RME neurons restrain head deflection. I then examined the calcium dynamics in RME and found the activity is correlated with, but not dependent on, dorsal-ventral head movement. Using a combination of neurophysiological, behavioral and optogenetic approaches, I found that the SMD neurons drive the calcium oscillation in RME via cholinergic neurotransmission. In return, the activated RME releases GABA, tuning down SMD activity via the B-type GABA receptor, and negatively regulates the head bending amplitude. The interaction between SMD and RME contributes to an excitation-inhibition balance in the motor system, which fine-tunes the bending angle and thus optimizes the phase velocity during forward movement. This oscillatory circuit suggests a parsimonious model for a small neural network to regulate the locomotory gait. The SMD motor neurons are also implicated in a sensori-motor circuit underlying olfactory learning. In Chapter 3, I investigate the plasticity of the circuit in pathogen-induced learning behavior. C. elegans learns to avoid the smell of pathogenic bacteria after being infected by the pathogen. I characterize a mutant that displays enhanced olfactory learning, eol-1, isolated from a forward genetic screen. eol-1 acts in the URX sensory neurons to inhibit learning. The protein product of eol-1 has many homologs in eukaryotes, including the mammalian protein Dom3Z implicated in pre-mRNA quality control. Expressing the mouse Dom3z in eol-1-expressing cells fully rescues the learning phenotype in eol-1 mutants, indicating that EOL-1 shares functional similarities with Dom3Z in regulating learning. Mutating the residues that are critical for the enzymatic activity of Dom3Z, and the equivalent residues in EOL-1, abolishes the function of these molecules in learning. These results provide insights into the function of a conserved protein in regulating experience-dependent behavioral plasticity. In summary, this dissertation aims to understand how a small nervous system regulates complex behavior in C. elegans. I show that the neural circuits underlying rhythmic locomotion share common properties, and evolutionarily conserved molecules have similar functions in regulating neural plasticity. Some of the principles uncovered in C. elegans may be generalizable and informative to our understanding of the human brain.Publication Functional Organization of a Neural Network for Aversive Olfactory Learning in Caenorhabditis elegans(Elsevier, 2010) Ha, Heon-ick; Hendricks, Michael Shelton; Shen, Yu Serena; Gabel, Christopher V.; Fang-Yen, Christopher M.; Qin, Yuqi; Shen, Kang; Zhang, Yun; Samuel, Aravi; Colón-Ramos, DanielMany animals use their olfactory systems to learn to avoid dangers, but how neural circuits encode naive and learned olfactory preferences, and switch between those preferences, is poorly understood. Here, we map an olfactory network, from sensory input to motor output, which regulates the learned olfactory aversion of Caenorhabditis elegans for the smell of pathogenic bacteria. Naive animals prefer smells of pathogens but animals trained with pathogens lose this attraction. We find that two different neural circuits subserve these preferences, with one required for the naive preference and the other specifically for the learned preference. Calcium imaging and behavioral analysis reveal that the naive preference reflects the direct transduction of the activity of olfactory sensory neurons into motor response, whereas the learned preference involves modulations to signal transduction to downstream neurons to alter motor response. Thus, two different neural circuits regulate a behavioral switch between naive and learned olfactory preferences.