Biology subjects

Lau, C. Y.

Publications and source records attributed to Lau, C. Y..

4 recordsLinked to original sources

bioRxiv2024

MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans

The muscleblind family of mRNA splicing regulators is conserved across species and regulate the development of muscles and the nervous system. However, how Muscleblind proteins regulate neuronal fate specification and neurite morphogenesis at the single-neuron level is not well understood. In this study, we found that the C. elegans Muscleblind/MBL-1 promotes axonal growth in the touch receptor neurons (TRNs) by regulating microtubule stability and polarity. Transcriptomic analysis identified dozens of MBL-1-controlled splicing events in genes related to neuronal differentiation or microtubule functions. Among the MBL-1 targets, the LIM-domain transcription factor mec-3 is the terminal selector for the TRN fate and induces the expression of many TRN terminal differentiation genes. MBL-1 promotes the splicing of the mec-3 long isoform, which are essential for TRN fate specification, and inhibits the short isoforms that have much weaker activities in activating downstream genes. MBL-1 promotes mec-3 splicing through three "YGCU(U/G)Y" motifs located downstream of the included exon, which is similar to the mechanisms used by mammalian Muscleblind and suggests a deeply conserved context-dependency of the splicing regulation. Interestingly, the expression of mbl-1 in the TRNs is dependent on the mec-3 long isoform, indicating a positive feedback loop between the splicing regulator and the terminal selector. Finally, through a forward genetic screen, we found that MBL-1 promotes neurite growth partly by inhibiting the DLK-1/p38 MAPK pathway. In summary, our study provides mechanistic understanding of the role of Muscleblind in regulating cell fate specification and neuronal morphogenesis.

developmental biology↗

bioRxiv2022

Dynamic evolution of recently duplicated genes in Caenorhabditis elegans

As a major origin of evolutionary novelties, gene duplication is a widespread phenomenon across species. However, the evolutionary force that determines the fate of duplicate genes is still under debate. Here, we studied the functional evolution of duplicate genes at both macroevolution and microevolution scales using the genomic sequences of eleven Caenorhabditis species and 773 C. elegans wild isolates. We found that compared to older duplicate genes and single-copy genes, recently duplicated gene copies showed rapid turnover, large genetic diversity, and signs of balancing and positive selection within the species. Young duplicate genes have low basal expression restricted to a few tissues but show highly responsive expression towards pathogenic infections. Recently duplicated genes are enriched in chemosensory perception, protein degradation, and innate immunity, implicating their functions in enhancing adaptability to external perturbations. Importantly, we found that young duplicate genes are rarely essential, while old duplicate genes have the same level of essentiality as singletons, suggesting that essentiality develops over a long time. Together, our work in C. elegans demonstrates that natural selection shapes the dynamic evolutionary trajectory of duplicate genes. SignificanceThe "evolution by gene duplication" theory suggests that gene duplications provide the genetic materials for mutation and selection to act upon, expand the repertoire of molecular functions, and enable evolutionary novelty. Although various models were proposed to describe the fate of duplicate genes, empirical evidence for these models is limited. We analyzed gene duplications in eleven nematode Caenorhabditis species and studied the intraspecific variation of these duplicate genes among C. elegans wild strains. We found that compared to older duplicate gens and single-copy genes, recently duplicated genes show rapid turnover, large genetic diversity, and strong signs of balancing and positive selection but rarely develop essential functions. Our results describe the evolutionary trajectory of duplicate genes shaped by natural selection.

evolutionary biology↗

bioRxiv2021

Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration

Growing evidence indicate that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases, such as Parkinsons disease (PD). The molecular mechanism underlying such microbe-host interaction is unclear. In this study, by feeding C. elegans expressing human -syn with E. coli knockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways, including curli formation, lipopolysaccharide assembly, adenosylcobalamin biosynthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA in E. coli reduced -syn-induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with -syn inside neurons and promoted -syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration in C. elegans models of AD, ALS, and HD and in human neuroblastoma cells.

neuroscience↗

bioRxiv2018

Life Inside A Dinosaur Bone: A Thriving Microbiome

Fossils were long thought to lack original organic material, but the discovery of organic molecules in fossils and sub-fossils, thousands to millions of years old, has demonstrated the potential of fossil organics to provide radical new insights into the fossil record. How long different organics can persist remains unclear, however. Non-avian dinosaur bone has been hypothesised to preserve endogenous organics including collagen, osteocytes, and blood vessels, but proteins and labile lipids are unstable during diagenesis or over long periods of time. Furthermore, bone is porous and an open system, allowing microbial and organic flux. Some of these organics within fossil bone have therefore been identified as either contamination or microbial biofilm, rather than original organics. Here, we use biological and chemical analyses of Late Cretaceous dinosaur bones and sediment matrix to show that dinosaur bone hosts a diverse microbiome. Fossils and matrix were freshly-excavated, aseptically-acquired, and then analysed using microscopy, spectroscopy, chromatography, spectrometry, DNA extraction, and 16S rRNA amplicon sequencing. The fossil organics differ from modern bone collagen chemically and structurally. A key finding is that 16S rRNA amplicon sequencing reveals that the subterranean fossil bones host a unique, living microbiome distinct from that of the surrounding sediment. Even in the subsurface, dinosaur bone is biologically active and behaves as an open system, attracting microbes that might alter original organics or complicate the identification of original organics. These results suggest caution regarding claims of dinosaur bone soft tissue preservation and illustrate a potential role for microbial communities in post-burial taphonomy.

paleontology↗