Search bioRxiv⌕ Search

Biology subjects

Velayudhan, S. S.

Publications and source records attributed to Velayudhan, S. S..

6 recordsLinked to original sources

Axin2L regulates planar cell polarity in Xenopus embryos

Axin proteins function as central scaffolds of the {beta}-catenin destruction complex in the Wnt/{beta}-catenin pathway that has been considered distinct from the planar cell polarity (PCP) pathway. Here, we show that dorsal expression of mutated Axin2L, a predominant Axin homolog in Xenopus early embryos, disrupts convergent extension movements and neural tube closure in a manner reminiscent of the mutations in vertebrate PCP genes. GFP-Axin2L becomes planar polarized in the epidermal cells adjacent to the folding neural plate and those surrounding a wound. Axin2L associated and colocalized with ADIP, a similarly polarized protein that is essential for neural tube morphogenesis and embryonic wound healing. Interference with Axin2L function abrogated Vangl2 accumulation at the anterior sides of neuroepithelial cells and impaired ciliogenesis in the gastrocoel roof plate. We propose that, in addition to the canonical Wnt pathway, Axin2L controls PCP signaling during vertebrate morphogenesis.

cell biology↗

Planar polarization of endogenous ADIP during Xenopus neurulation

Coordinated cell polarity and force-responsive protein localization are essential for tissue morphogenesis, yet how embryonic cells sense forces and respond to mechanical cues remains a challenging question. Afadin- and alpha-actinin-binding protein (ADIP) has been implicated in microtubule minus-end anchoring, centrosome maturation and ciliogenesis. ADIP is also proposed to associate with the actomyosin cortex and regulate collective cell migration. ADIP behaves as a mechanosensitive planar cell polarity (PCP) protein when overexpressed in Xenopus embryos, but the distribution and regulation of endogenous ADIP has been unknown. Here we show that ADIP is present in early ectoderm as randomly distributed puncta that rapidly reorganize and polarize during epithelial wound repair. Endogenous ADIP also becomes enriched and planar polarized in the anterior neural plate towards the midline, consistent with its regulation by mechanical forces that operate during neural tube closure. ADIP polarization is attenuated by depletion of the core PCP component Diversin/Ankrd6, in agreement with the proposed interaction between the two proteins during PCP establishment. Finally, pharmacological disruption of microtubules, F-actin, and nonmuscle myosin II eliminates ADIP polarization in the neuroectoderm, indicating roles for microtubules and actomyosin networks in PCP. Together, these findings suggest that endogenous ADIP senses mechanical cues via the cytoskeletal machinery and functions in the context-dependent manner to control collective cell behaviors during vertebrate morphogenesis.

developmental biology↗

Deciphering the Survival Strategies of the Entomopathogenic Nematode Steinernema carpocapsae Using Rapid Desiccation Assisted by Nanoparticle-Based Emulsion

Water retention is essential for survival under desiccating conditions, especially for entomopathogenic nematodes (EPNs) used as biocontrol agents. Foliar application of EPNs causes rapid desiccation (RD), severely reducing their survival and efficacy. We investigated the physiological and molecular responses of Steinernema carpocapsae to RD, delivered in a novel nanoparticle-stabilized emulsion to improve tolerance under variable humidity. We hypothesized that the formulation would enhance EPNs survival, by promoting early stress-responsive pathways and water-retention mechanisms. Formulated nematodes exhibited delayed water loss and increased survival under low humidity compared with non-formulated controls. The emulsion mitigated RD by enhanced hydration retention and reduced water loss, effects that were strongly associated with differential trehalose accumulation. In addition, maintenance of basement membrane integrity and cytoskeletal organization, emerged as a critical component of desiccation. These findings advance understanding of RD tolerance in EPNs and demonstrate how tailored formulation strategies can protect biocontrol agents under desiccation stress.

developmental biology↗

Mechanosensitive localization of Diversin highlights its function in vertebrate morphogenesis and planar cell polarity

Diversin is a vertebrate homolog of the core planar cell polarity (PCP) protein Diego. Here we studied the function of Diversin in Xenopus embryo morphogenesis and its subcellular localization at different locations in superficial ectoderm cells. Depletion of Diversin in the neuroectoderm inhibited apical domain size and neural tube closure and disrupted the polarized localization of endogenous Vangl2, another PCP protein. Whereas Diversin puncta were randomly distributed in early ectoderm, they acquired planar polarity in the neuroectoderm in a stage- and position-specific manner. We find that Diversin is accumulated at the cell junctions adjacent to apically constricting cells at the Xenopus neural plate border and the gastrula blastopore lip. Moreover, Diversin cytoplasmic puncta redistributed in the direction of the pulling forces from the cells with constricting apical domains, suggesting a mechanosensitive process. PCP complexes of Dishevelled (Dvl2) and Diversin or the mechanosensitive adaptor ADIP exhibited planar polarity in the neural plate and the wound edge and promoted wound healing. We propose that Diversin- and Dvl2-containing PCP complexes control morphogenesis in a tension-dependent manner.

cell biology↗

Mechanical cues organize planar cell polarity during vertebrate morphogenesis and embryonic wound repair

Planar cell polarity (PCP) is a phenomenon of coordinated cell orientation in many epithelia and is required for early morphogenetic events, such as vertebrate gastrulation or neural tube closure that place embryonic tissues in their proper locations. Known PCP complexes segregate to opposite edges of each cell due to regulatory feedback interactions, however, whether and how PCP is connected to the tension-sensing machinery has been elusive. Here we observed dynamic polarization of Afadin- and -Actinin-interacting protein (ADIP) in the epithelia adjacent to the involuting marginal zone and the folding neural plate of Xenopus embryos, suggesting that it is controlled by mechanical cues. Supporting this hypothesis, ADIP puncta relocated in response to the pulling forces of neighboring ectoderm cells undergoing apical constriction. Moreover, ADIP puncta rapidly polarized in embryos subjected to stretching and during embryonic wound healing. ADIP formed a mechanosensitive complex with the PCP protein Diversin that was distinct from known core PCP complexes and required for wound repair. We propose that mechanically controlled planar polarization of the ADIP-Diversin complex guides cell behaviors in normal morphogenesis and during wound healing. HighlightsO_LIADIP is a mechanosensing protein that is planar polarized together with Diversin in epithelia during morphogenesis and wound repair C_LIO_LIEpithelial wound healing redistributes ADIP-containing complexes towards the wound. C_LIO_LIADIP and Diversin are interdependent and form a complex regulating morphogenesis and wound healing C_LIO_LIPositive regulatory feedback between mechanical forces and PCP signaling drives morphogenesis C_LI

developmental biology↗

Adult-specific trimethylation of histone H3 lysine 4 is prone to dynamic changes with aging in C. elegans somatic cells

Tri-methylation on histone H3 lysine 4 (H3K4me3) is associated with active gene expression but its regulatory role in transcriptional activation is unclear. Here we used Caenorhabditis elegans to investigate the connection between H3K4me3 and gene expression regulation during aging. We uncovered around 30% of H3K4me3 enriched regions to show significant and reproducible changes with age. We further showed that these age-dynamic H3K4me3 regions largely mark gene-bodies and are acquired during adult stages. We found that these adult-specific age-dynamic H3K4me3 regions are correlated with gene expression changes with age. In contrast, H3K4me3 marking established during developmental stages remained largely stable with age, even when the H3K4me3 associated genes exhibited RNA expression changes during aging. Moreover, we found that global reduction of H3K4me3 levels results in significantly decreased RNA expression of genes that acquire H3K4me3 marking in their gene-bodies during adult stage, suggesting that altered H3K4me3 levels with age could result in age-dependent gene expression changes. Interestingly, the genes with dynamic changes in H3K4me3 and RNA levels with age are enriched for those involved in fatty acid metabolism, oxidation-reduction, and stress response. Therefore, our findings revealed divergent roles of H3K4me3 in gene expression regulation during aging, with important implications on physiological relevance.

molecular biology↗