Biology subjects

Teasdale, L.

Publications and source records attributed to Teasdale, L..

3 recordsLinked to original sources

bioRxiv2026

SYNGAP1 haploinsufficiency disrupts early neurodevelopment and accelerates intrinsic neuronal maturation in human patient-derived models

SYNGAP1 developmental and epileptic encephalopathy (DEE) is a severe neurodevelopmental disorder characterised by intellectual disability, developmental delay, and refractory epilepsy caused by heterozygous variants in SYNGAP1, which encodes Synaptic Ras GTPase-activating protein 1. While SYNGAP1 is best known for its role at the postsynaptic density, increasing evidence indicates that haploinsufficiency also disrupts early neurodevelopment. Here, we used patient-derived induced pluripotent stem cell (iPSC) models to investigate early neurodevelopmental and neuronal phenotypes associated with SYNGAP1 haploinsufficiency. iPSCs derived from a female patient carrying the frameshift variant p.Leu150Valfs*6 were differentiated into two complementary models: micropatterned neural rosettes representing early neuroepithelial organisation and NGN2-induced excitatory neurons representing postmitotic functional development. Patient-derived neural rosettes displayed enlarged, dysmorphic lumens, indicating disrupted neuroepithelial organisation at the earliest stages of brain development. Transcriptomic profiling revealed widespread dysregulation of genes involved in neurodevelopment, cell adhesion and ion channel regulation, including coordinated downregulation of protocadherin family members. Whole-cell patch-clamp electrophysiology demonstrated reduced input resistance, larger action potential amplitudes, and increased inward and outward current densities, consistent with accelerated intrinsic neuronal maturation rather than generalized hyperexcitability. Together, these complementary findings demonstrate that SYNGAP1 haploinsufficiency disrupts early human brain development and accelerates intrinsic neuronal maturation, with pathogenic mechanisms emerging before synaptogenesis and extending beyond SYNGAP1s established synaptic role.

neuroscience↗

bioRxiv2024

The 1001G+ project: A curated collection of Arabidopsis thaliana long-read genome assemblies to advance plant research

Arabidopsis thaliana was the first plant for which a high-quality genome sequence became available. The publication of the first reference genome sequence almost 25 years ago was already accompanied by genome-wide data on sequence polymorphisms in another accession, or naturally occurring strain. Since then, inventories of genome-wide diversity have been generated at increasingly precise levels. High-density genotype data for A. thaliana, including those from the 1001 Genomes Project, were key to demonstrating the enormous power of GWAS in inbred populations of wild plants, and the comparison of intraspecific polymorphism with interspecific divergence has illuminated many aspects of plant genome evolution. Over the past decade, an increasing number of nearly complete genome sequences have been published for many more accessions. Here, we highlight the diversity of a curated collection of previously published and so far unpublished genome sequences assembled using different types of long reads, including PacBio Continuous Long Reads (CLR), PacBio High Fidelity (HiFi) reads, and Oxford Nanopore Technologies (ONT) reads. This 1001 Genomes Plus (1001G+) resource is being made available at http://1001genomes.org. We invite colleagues with yet unpublished genome assemblies from A. thaliana accessions to contribute to this effort.

genomics↗

bioRxiv2023

An atypical endomembrane localized CNL-type immune receptor with a conserved deletion in the N-terminal signaling domain functions in cell death and immunity

Plants have evolved intracellular nucleotide-binding leucine rich repeat receptors (NLRs) to induce a superior immune response. Upon activation, coiled-coil (CC) domain containing NLRs (CNLs) oligomerize to form apparent cation channels that promote calcium influx and cell death induction, with the alpha-1 helix of the individual CC domains penetrating membranes. Some members of a monophyletic subclass of CNLs, the ancient and autonomous NLRs (ANLs), are characterized by putative N- myristoylation and S-acylation sites at the N-terminus of their CCG10/GA domain, potentially mediating permanent membrane association. Whether these Potentially Membrane Localized NLRs (PMLs) mediate cell death upon activation in a similar way as reported for other CNLs has been unknown. We integrated phylogenetic, cell- biological, and functional studies to uncover the cell death function of an atypical but conserved Arabidopsis PML, PML5, which has a 113 amino acid deletion in its CCG10/GA domain. Active PML5 oligomers localize in Golgi membranes and the tonoplast, changes vacuolar morphology, and induce cell death, with the short N- terminus being sufficient for cell death. Mutant analysis supports a potential key role of PMLs in plant immunity. Similar deletions as in Arabidopsis PML5 are found in several Brassicales paralogs, pointing to the evolutionary importance of this innovation. PML5 is thus a naturally occurring CNL variant with a minimal signaling domain and its further study should help in understanding the functional importance of this minimal domain for NLR signaling.

plant biology↗