Biology subjects

Tzeng, C. P.

Publications and source records attributed to Tzeng, C. P..

3 recordsLinked to original sources

bioRxiv2023

Wnt signaling and contact-mediated repulsion shape sensory dendritic fields

The complete and non-redundant coverage of sensory tissues by neighboring neurons enables effective detection of stimuli in the environment. How the neurites of adjacent neurons establish their boundaries to achieve this completeness in coverage remains incompletely understood. Here, we use distinct fluorescent reporters to study two neighboring sensory neurons with complex dendritic arbors, FLP and PVD, in C. elegans. We quantify the sizes of their dendritic fields, and identify CWN-2/Wnt and LIN-17/Frizzled as a ligand and receptor that regulate the relative dendritic field sizes of these two neurons. Loss of either cwn-2 or lin-17 results in complementary changes in the size of the dendritic fields of both neurons; the FLP arbor expands, while that of PVD shrinks. Using an endogenous knock-in mNeonGreen-CWN-2/Wnt, we find that CWN-2/Wnt is localized along the path of growing FLP dendrites. Dynamic imaging shows a significant braking of FLP dendrite growth upon CWN-2/Wnt contact. We find that LIN-17/Frizzled functions cell-autonomously in FLP to limit dendritic field size and propose that PVD fills the space left by FLP through contact-induced retraction. Our results reveal that interactions of dendrites with adjacent dendrites and with environmental cues both shape the boundaries of neighboring dendritic fields. Highlights{square} Secreted Wnt CWN-2 and cell-autonomous activity of neuronal LIN-17/Frizzled receptors restrict FLP dendritic field sizes {square}Endogenously tagged CWN-2/Wnt is punctate and visible in the same plane of growing FLP dendrites {square}Growth of developing FLP dendrites is inhibited upon contact with extracellular CWN-2/Wnt and with PVD dendrites

neuroscience↗

bioRxiv2023

Activity-Induced MeCP2 Phosphorylation Regulates Retinogeniculate Synapse Refinement

Mutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelopmental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of MeCP2 causes miswiring of neural circuits due to defects in the brains capacity to respond to changes in neuronal activity and sensory experience. Here we show that MeCP2 is phosphorylated at four residues in the brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dependent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is initially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from that previously reported for Mecp2 null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-induced phosphorylation of MeCP2 is critical for the proper timing of retinogeniculate synapse maturation specifically during the early postnatal period. SIGNIFICANCE STATEMENTRett syndrome (RTT) is an X-linked neurodevelopmental disorder that predominantly affects girls. RTT is caused by loss of function mutations in a single gene MeCP2. Girls with RTT develop normally during their first year of life, but then experience neurological abnormalities including breathing and movement difficulties, loss of speech, and seizures. This study investigates the function of the MeCP2 protein in the brain, and how MeCP2 activity is modulated by sensory experience in early life. Evidence is presented that sensory experience affects MeCP2 function, and that this is required for synaptic pruning in the brain. These findings provide insight into MeCP2 function, and clues as to what goes awry in the brain when the function of MeCP2 is disrupted.

neuroscience↗

bioRxiv2019

PESCA: A scalable platform for the development of cell-type-specific viral drivers

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.\n\nOne sentence summaryHighly paralleled functional evaluation of enhancer activity in single cells generates new cell-type-specific tools with broad medical and scientific applications.

neuroscience↗