Biology subjects

Higgs, V.

Publications and source records attributed to Higgs, V..

3 recordsLinked to original sources

bioRxiv2026

Gαi2 coordinates neuronal microtubule and neurofilament networks to regulate axon initiation in vivo

Neurons possess a highly polarised morphology, established through axon formation. However, the mechanisms regulating stable axon initiation during embryonic development remain poorly understood. Here, using fixed-tissue super-resolution and high-resolution live-tissue imaging in developing chick spinal cord, we demonstrate that the multifunctional G-protein Gi2 coordinates the interconnected neurofilament and microtubule networks to achieve stable axon outgrowth. Before axon initiation, microtubule network orientation shifts towards the site of the future axon where coiled Gi2-associated neurofilaments accumulate asymmetrically before unfurling into the initiating axon behind microtubules. Crucially, Gi2 is associated with neurofilaments and microtubules at points of contact. Gi2 depletion reduces engagement between these cytoskeletal networks, and leads to impaired passage of neurofilaments into initiating axons and disrupted axon outgrowth, supporting a role for Gi2 in regulating microtubule-driven incorporation of neurofilaments in nascent axons. These findings advance mechanistic understanding of polarity establishment and offer an enriched view of cytoskeletal regulation during axon formation.

developmental biology↗

bioRxiv2025

A depositional taphonomy model for sedimentary ancient DNA based on biotic profiles of contrasting sedimentation regimes

Sedimentary ancient DNA (sedaDNA) has become an important tool in Quaternary Science, but still little is understood of its taphonomy and whether sedaDNA represents the local vicinity or originates from distant sources. Here we show key insights can be made about the origins of sedaDNA by integrating sedimentological and sedaDNA data into a sediment influx depositional model. We reconstruct contrasting taphonomic regimes of lacustrine, alluvial, terrestrial and permafrost systems. Lacustrine systems show signals of regional catchment sources of sedaDNA, while alluvial, terrestrial and permafrost systems show a greater influence of DNA from the immediate local environment. However, there is a prevalence of mixed ecosystem signals which may span a broad temporal timeframe if sediment reworking has occurred. The ability to distinguish between local and distal sources of sedaDNA is of major importance in the interpretation of taxonomic profiles to reconstruct palaeoenvironments.

ecology↗

bioRxiv2024

Impact of intragenic NRXN1 deletions on early cortical development

BackgroundDeletions in NRXN1 are strongly associated with neurodevelopmental and psychiatric conditions. While exonic deletions are well-studied, intragenic deletions, particularly in intron 5, are less understood and generally consider benign. Recent studies show exonic deletions impact isoform diversity during neurodevelopment, affecting neurogenesis and neuronal function. However, whether intragenic deletions impact isoform expression and neurodevelopment remains underexplored. MethodsWe used hiPSCs from typically developing individuals (control) and those with NRXN1 intron 5 deletions to study neurodevelopment. HiPSCs were differentiated towards a cortical fate, with NRXN1 isoform expression, molecular differences, and neuronal morphology examined. ResultsWe observed distinct NRXN1 isoform expression dynamics during early neurodevelopment, with two expression peaks post-neuronal induction and NRXN1{beta} being most highly expressed. Both NRXN1 deletion and control lines showed similar acquisition of regional and cell fate identity, but significant differences in NRXN1 isoform expression were observed between deletion and control lines, and between deletion lines. RNA sequencing revealed genotype-dependent alterations, particularly in pathways related to synaptic function and neuronal morphology. Consistent with these findings, NRXN1 deletion lines exhibited altered dendrite outgrowth, with variations between deletion lines. ConclusionsOur results indicate a potential role for intron 5 in controlling NRXN1 isoform expression during neurodevelopment. Alterations in gene expression profiles, correlated with morphological changes, suggest a role for NRXN1 isoforms in shaping dendritic morphology. Molecular and cellular differences observed between lines with identical intronic deletions suggest that additional factors, such as genetic background or biological sex, may also play an important role in these phenotypes. Collectively, these findings indicate that NRXN1 intronic deletions are not benign, influencing isoform expression, cellular phenotypes, and neurodevelopment.

neuroscience↗