Biology subjects

Lu, Y.-M.

Publications and source records attributed to Lu, Y.-M..

3 recordsLinked to original sources

bioRxiv2026

Neuron-intrinsic and glial pathways regulate sensory cilia regeneration in adult C. elegans

Primary cilia are microtubule-based organelles that mediate cellular responses to environmental cues. Although cilia disassemble and reassemble upon cell cycle entry and exit, respectively, in dividing cells, it remains unclear whether postmitotic cells such as neurons can regenerate these structures in vivo following injury to restore function, and whether this process recapitulates developmental ciliogenesis. Here we show that a subset of sensory neuron cilia in adult C. elegans regrows following conditional truncation and restores neuronal functions. This regeneration is regulated by both cell-intrinsic and extrinsic mechanisms that are in part distinct from those employed during embryonic ciliogenesis. We find that the conserved ciliogenic DAF-19 RFX transcription factor is dispensable for cilia maintenance in the adult but is required for regeneration, in part via transcriptional upregulation of a subset of ciliary intraflagellar transport (IFT) genes. We further identify the DLK-1 dual leucine-zipper kinase and the CEBP-1 C/EBP transcription factor, previously implicated in axon regeneration, as necessary for efficient cilia regrowth but not for developmental ciliogenesis. We show that cebp-1 expression is induced during cilia truncation and regrowth and that this induction is also DAF-19-dependent. Finally, we show that cilia truncation and regeneration dynamics vary in a neuron type-specific manner and are modulated by signals from surrounding glia. Our results establish that the cilia of mature neurons can regenerate and recover functions in vivo and identify conserved pathways that regulate this process in adult animals.

cell biology↗

bioRxiv2026

Stereotypical interciliary contacts in a C. elegans sense organ

Physical interactions among cells and their processes are critical for intercellular communication and the generation of ordered tissue patterns. Primary cilia projecting from the cell surface have recently been shown to form contacts with the processes of diverse cell types, as well as with other cilia, in the brain and other organs. Whether these ciliary contacts are established in an instructive manner or are formed passively due to physical proximity is unclear. Ultrastructural analyses previously showed that the cilia of a subset of sensory neurons in the head amphid organs of C. elegans exhibit interciliary contacts within a glia-defined channel. Here we show that these ciliary contact patterns are stereotyped and can be established in the absence of neighboring cilia, indicating that these associations may not simply reflect relative positioning within the amphid channel. We show that mutations in genes implicated in ciliary protein trafficking, ciliary membrane phospholipid composition, and cilia-cell interactions disrupt cilia structure and/or interciliary contacts, and that in a subset of mutants, cilia with altered morphologies can nevertheless establish correct contacts. Together, our findings suggest that cilia-cilia interactions within a sense organ are established via instructive mechanisms, and raise the possibility that cellular functions may be modulated by cilia-mediated intercellular communication. SummaryThis work investigates how primary cilia, structures that detect and transmit signals, form contacts with one another in a head sensory organ of the nematode Caenorhabditis elegans. The authors found that these contacts follow consistent patterns and can form even when neighboring cilia are absent, suggesting they are actively established rather than occurring due to physical proximity. The authors identified mutations in genes that regulate cilia protein content, membrane composition, and cellular adhesion that disrupt cilia structure or contacts. These findings suggest that cilia-cilia interactions are regulated, raising the possibility that they play important roles in cell communication.

cell biology↗

bioRxiv2024

Editing of endogenous tubulins reveals varying effects of tubulin posttranslational modifications on axonal growth and regeneration

Tubulin posttranslational modifications (PTMs) modulate the dynamic properties of microtubules and their interactions with other proteins. However, the effects of tubulin PTMs were often revealed indirectly through the deletion of modifying enzymes or the overexpression of tubulin mutants. In this study, we directly edited the endogenous tubulin loci to install PTM-mimicking or -disabling mutations and studied their effects on microtubule stability, neurite outgrowth, axonal regeneration, cargo transport, and sensory functions in the touch receptor neurons of Caenorhabditis elegans. We found that the status of {beta}-tubulin S172 phosphorylation and K252 acetylation strongly affected microtubule dynamics, neurite growth, and regeneration, whereas -tubulin K40 acetylation had little influence. Polyglutamylation and detyrosination in the tubulin C-terminal tail had more subtle effects on microtubule stability likely by modulating the interaction with kinesin-13. Overall, our study systematically assessed and compared several tubulin PTMs for their impacts on neuronal differentiation and regeneration and established an in vivo platform to test the function of tubulin PTMs in neurons.

cell biology↗