Biology subjects

Sierra, C.

Publications and source records attributed to Sierra, C..

3 recordsLinked to original sources

bioRxiv2023

A novel regulatory mechanism of actin cytoskeleton dynamics through a neural microexon in DAAM1 is necessary for memory formation

Actin cytoskeleton dynamics is critical for nervous system development and function, yet the role of alternative splicing in controlling these processes is poorly understood. A highly conserved subset of neuronal-specific microexons coordinates fundamental aspects of nervous system biology. A subset of these exons is enriched in genes involved in actin cytoskeleton, yet their functions are unknown. Here, we focus on a microexon in DAAM1, a member of the formin-homology-2 (FH2) domain class of proteins, which have diverse functions associated with the reorganization of the actin cytoskeleton. Remarkably, splicing of the microexon extends the linker region of the DAAM1 FH2 domain and leads to qualitative and quantitative changes in actin polymerization. Deletion of the microexon results in neuritogenesis defects and increased calcium influx in differentiated neurons. Moreover, mice harboring the deletion exhibit postsynaptic defects, reduced number of immature dendritic spines, impaired long-term potentiation, and deficits in memory formation. These deficits are associated with increased RHOA/ROCK signaling, pivotal in controlling actin-cytoskeleton dynamics, and were rescued by treatment with a ROCK inhibitor. We thus demonstrate that a conserved neuronal microexon in DAAM1 is critical for controlling actin dynamics through the RHOA/ROCK signaling pathway and is necessary for normal cognitive functioning.

neuroscience↗

bioRxiv2021

Single nucleus RNA-seq in the hippocampus of a Down syndrome mouse model reveals new key players in memory

Down syndrome (DS) is the most common genetic cause of intellectual disability. Even though great advances in the last decades have allowed better delineation of its pathogenetic mechanisms, its cellular and molecular bases are still poorly understood. To evaluate the consequences of chromosome aneuploidy on the hippocampus, we analyzed single-nucleus transcriptional profiles of the DS mouse model Ts65Dn. Our data revealed abnormal cell composition specifically of the Ts65Dn dentate gyrus and of specific subtypes of interneurons, without major changes in CA1 or CA3. We found that trisomy results in a highly cell-type specific global alteration of the transcriptome and detected previously undefined differentially expressed genes in specific neuronal populations. We identified the long-non-coding gene Snhg11 to be specifically downregulated in the trisomic dentate gyrus and provide evidence for its involvement in hippocampal-dependent cognitive phenotypes, possibly contributed by impaired adult neurogenesis.

neuroscience↗

bioRxiv2021

Non-structural carbohydrate concentrations in woody organs, but not leaves, of temperate and tropical tree angiosperms are independent of the "fast-slow" plant economic spectrum

Background and AimsCarbohydrate reserves play a vital role in plant survival during periods of negative carbon balance. Considering active storage of reserves, there is a trade-off between carbon allocation to growth and to reserves and defense. A resulting hypothesis is that allocation to reserves exhibits a coordinated variation with functional traits associated with the fast-slow plant economics spectrum. MethodsWe tested the relationship between non-structural carbohydrates (NSC) of tree organs and functional traits using 61 angiosperm tree species from temperate and tropical forests with phylogenetic hierarchical Bayesian models. Key ResultsOur results provide evidence that NSC concentrations in woody organs and plant functional traits are largely decoupled, meaning that species resilience is unrelated to their position on the fast-slow plant economics spectrum. In contrast, we found that variation between NSC concentrations in leaves and the fast-slow continuum was coordinated, as species with higher leaf NSC had traits values associated with resource conservative species such as lower SLA, lower Amax, and high wood density. We did not detect an influence of leaf habit on the variation of NSC concentrations in tree organs. ConclusionsEfforts to predict the response of ecosystems to global change will need to integrate a suite of plant traits, such as NSC concentrations in woody organs, that are independent of the fast-slow spectrum and that capture how species respond to a broad range of global change factors.

plant biology↗