Biology subjects

Collins, S. C.

Publications and source records attributed to Collins, S. C..

6 recordsLinked to original sources

bioRxiv2026

Hippocampal Ring Finger Protein 10-dependent signaling supports cognitive flexibility

The ability to flexibly adapt behavior to changing environmental contingencies is a core component of brain function and relies on experience-dependent remodeling of neural circuits. While cognitive flexibility has been primarily attributed to prefrontal-striatal networks, the contribution of hippocampus and their underlying molecular substrates remains less understood. Here, we show that the dorsal hippocampus has a key role in cognitive flexibility. In particular, Ring Finger Protein 10 (RNF10)-mediated signaling, linking activation of synaptic NMDARs to specific transcriptional programs in the dorsal CA1, is necessary for cognitive flexibility. In fact, in vivo downregulation, through gene deletion and silencing of RNF10, resulting in impaired long-term synaptic plasticity, suppressed cognitive flexibility. This was reflected in the impaired ability to disengage from previously acquired contextual, visual, and spatial information and to adapt behavior to changed context. Overall, our results identified RNF10 as a key in vivo player necessary for the balance between cognitive stability and flexibility.

animal behavior and cognition↗

bioRxiv2025

Lipid transport is necessary for neocortical lamination

We previously described the Alkuraya-Ku[c]inskas syndrome, a disorder associated with biallelic variants in BLTP1 (bridge-like lipid transfer protein), a.k.a. KIAA1109. The majority of probands die perinatally with corpus callosum agenesis, ventriculomegaly and arthrogryposis. Homozygous ablation of mouse Bltp1 resulted in similar preweaning lethality. Here, we describe ten novel patients expanding the characterization of this syndrome at the mild end of the phenotypic spectrum. To model this syndrome, we engineered Emx1-Cre-mediated conditional knockouts (cKO) in which Bltp1 expression is only removed in cortical and hippocampal neurons. This restricted ablation of Bltp1 recapitulated the preweaning lethality observed in the constitutional knockouts, suggesting that lack of BLTP1 expression in neurons is sufficient to cause death. Homozygous cKO presented a complete agenesis of the corpus callosum, a smaller anterior commissure, a malformed hippocampus and a reduced thickness of the cortical plate with a complete lack of defined structural layers and absence of radial glial and intermediate neural progenitors and mature neurons. As BLTP1 was shown to be a barrel-shaped tube containing lipids, we compared the amount of lipid species in the cKO and their control littermates cortexes. We observed significant depletions of ether-linked phosphatidylethanolamines and triglycerides and accumulations of sphingomyelins and hexosylceramides in cKOs. Our results are consistent with the recent description of BLTP1 as a tubular protein that transports phospholipids between the endoplasmic reticulum and the plasma membrane. They suggest that non-vesicular lipid transport is essential for neocortical and cerebellar lamination. Consistent with a BLTP1 role in cortex development we show that heterozygous carriers of a BLTP1 truncation variant presented a decrease in peripheral cortical grey matter suggesting an autosomal dominant inheritance pattern beside the already described autosomal recessive.

genetics↗

bioRxiv2022

Diversification is correlated with temperature in white and sulfur butterflies

Temperature is thought to be a key variable explaining global patterns of species richness. However, to investigate this relationship carefully, it is necessary to study clades with broad geographic ranges that are comprised of species inhabiting diverse biomes with well- characterized species ranges. In the present study, we investigate the link between temperature and diversification in the butterfly family Pieridae (sulfurs and whites) by combining Next Generation sequences and published molecular data with fine-grained distribution information. After building the most comprehensive phylogeny of the group, with almost 600 species and all higher taxa (subfamilies, tribes and subtribes), we found strong support for the following relationships within the family: Dismorphiinae + (Coliadinae + (Pseudopontiinae + Pierinae)). With a curated distribution dataset of over 800,000 occurrences, we conducted multiple comparative phylogenetic analyses that provided strong evidence that species in environments with more stable daily temperatures or with cooler maximum temperatures in the warm seasons have higher diversification rates. We also found a positive correlation between speciation and extinction with paleotemperature: as global temperature decreased through geological time, so did diversification rates. Although many studies demonstrate higher diversity in the tropics, we have been able to identify specific climate variables associated with changes in diversification, while also inferring the most robust and well sampled phylogenomic framework for Pieridae to date.

evolutionary biology↗

bioRxiv2022

Mouse and cellular models of KPTN-related disorder implicate mTOR signalling in cognitive and progressive overgrowth phenotypes

KPTN-related disorder (KRD) is an autosomal recessive disorder associated with germline variants in KPTN (kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KRD, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn-/- mice display many of the key KRD phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. Assessment of affected individuals has identified concordant selectivity of cognitive deficits, postnatal onset of brain overgrowth, and a previously unrecognised KPTN dosage-sensitivity, resulting in increased head circumference in their heterozygous parents. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape, and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated iPSC models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. Increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KRD in the broader group of mTORC1 related disorders affecting brain structure, cognitive function, and network integrity.

genetics↗

bioRxiv2022

Evolution and diversification dynamics of butterflies

Butterflies are a diverse and charismatic insect group that are thought to have diversified via coevolution with plants and in response to dispersals following key geological events. These hypotheses have been poorly tested at the macroevolutionary scale because a comprehensive phylogenetic framework and datasets on global distributions and larval hosts of butterflies are lacking. We sequenced 391 genes from nearly 2,000 butterfly species to construct a new, phylogenomic tree of butterflies representing 92% of all genera and aggregated global distribution records and larval host datasets. We found that butterflies likely originated in what is now the Americas, [~]100 Ma, shortly before the Cretaceous Thermal Maximum, then crossed Beringia and diversified in the Paleotropics. The ancestor of modern butterflies likely fed on Fabaceae, and most extant families were present before the K/Pg extinction. The majority of butterfly dispersals occurred from the tropics (especially the Neotropics) to temperate zones, largely supporting a "cradle" pattern of diversification. Surprisingly, host breadth changes and shifts to novel host plants had only modest impacts.

evolutionary biology↗

bioRxiv2019

To mate, or not to mate: The evolution of reproductive diapause facilitates insect radiation into African savannahs in the Late Miocene

O_LIMany tropical environments experience cyclical seasonal changes, frequently with pronounced wet and dry seasons, leading to a highly uneven temporal distribution of resources. Short-lived animals inhabiting such environments often show season-specific adaptations to cope with alternating selection pressures.\nC_LIO_LIAfrican Bicyclus butterflies show strong seasonal polyphenism in a suite of phenotypic and life-history traits, and their adults are thought to undergo reproductive diapause associated with the lack of available larval host plants during the dry season.\nC_LIO_LIUsing three years of longitudinal field data for three species in Malawi, dissections demonstrated that one forest species reproduces continuously whereas two savannah species undergo reproductive diapause in the dry season, either with or without pre-diapause mating. Using additional data from field-collected and museum samples, we then documented the same three mating strategies for a further 37 species.\nC_LIO_LIPhylogenetic analyses indicated that the ancestral state was a non-diapausing forest species, and that habitat preference and mating strategy evolved in a correlated fashion.\nC_LIO_LIBicyclus butterflies underwent rapid diversification during the Late Miocene, coinciding with expansions into more open savannah habitat. We conclude that the ability to undergo reproductive diapause was a key trait that facilitated colonization and eventual radiation into savannahs in the Late Miocene.\nC_LI

evolutionary biology↗