Biology subjects

Ferraro, T.

Publications and source records attributed to Ferraro, T..

5 recordsLinked to original sources

bioRxiv2026

Persistent and recyclable myosin II minifilaments drive cortical contractility in the early C. elegans embryo

Non-muscle myosin II is a key regulator of cell and tissue morphogenesis, yet the cortical dynamics of myosin minifilaments in vivo remain poorly understood. Here, we combine SIM-TIRF and single-molecule TIRF microscopy to characterize the structure and dynamics of myosin minifilaments in an early developing embryo. High-temporal-resolution SIM-TIRF imaging revealed diverse minifilament behaviors, including partition-like events, long-range alignment of multiple minifilaments into collective structures we called proto-stress fibers, partial unbinding, and sequential unbinding and rebinding to the cortex. Photoconversion experiments showed that minifilaments persist as intact units after cortical unbinding, diffuse through the cytoplasm, and can be recycled over long distances rather than disassembling upon detachment. Despite these dynamic behaviors, minifilaments are predominantly stationary when bound to actin. Numerical simulations demonstrated that this static behavior is essential to sustain cortical stress within a continuously remodeling actin network. Using myosin motor-domain mutants, we further investigated the contribution of motor activity to these behaviors. Together, our results reveal that myosin minifilaments can persist as stable units while cycling between the cortex and cytoplasm, and that their predominantly static behavior when bound to actin enables sustained force generation in a continuously renewing cortical network. These findings provide new insights into myosin organization, recycling, and force generation during early embryonic development.

cell biology↗

bioRxiv2024

Astrocyte-derived extracellular matrix proteins regulate synapse remodeling in stress-induced depression

Major depressive disorder (MDD) is a common mood condition affecting multiple brain regions and cell types. Changes in astrocyte function contribute to depressive-like behaviors. However, while neuronal mechanisms driving MDD have been studied in some detail, molecular mechanisms by which astrocytes promote depression have not been extensively explored. To uncover astrocyte contributions to MDD, we subjected male mice to chronic social defeat stress precipitated by encounters with a dominant male. Animals exposed to this treatment exhibit symptoms indicative of MDD, including reduced social interactions, anxiety, despair, and anhedonia. We then measured astrocyte translating mRNA expression changes in mice that underwent chronic social defeat and control animals using ribosome affinity purification. Bioinformatic analyses reveal significant alterations in the prefrontal cortex (PFC), consistent with previous studies implicating this brain region in MDD. Expression of genes encoding extracellular matrix (ECM) proteins, cell-cell interaction proteins, and proteins controlling glutamatergic synaptic function are significantly altered. These changes correlate with perturbation of glutamatergic transmission, measured by electrophysiology, and increased synaptic cleft size. Among ECM genes, increased expression of mRNA encoding the synaptic remodeling protein secreted protein acidic and rich in cysteine (Sparc) correlates the most with the depressive phenotype. Furthermore, presence of SPARC and other ECM proteins in synaptosomes is also increased and overexpressing Sparc in PFC partially alleviates stress symptoms. Our results raise the possibility that increased expression of Sparc may be a natural protective mechanism against stress-induced synaptic dysfunction in depression.

neuroscience↗

bioRxiv2024

Repeated extrinsic and anisotropic mechanical inputs promote polarized adherens junction elongation

A key challenge in development is understanding how complex organisms physically coordinate the morphogenesis of multiple tissues. Here, using biophysical approaches, we investigate how muscles under the epidermis specifically stimulate the extension of anterior-posterior (AP-oriented) epidermal adherens junctions during late C. elegans embryonic elongation. First, light-sheet imaging shows that asynchronous patterns of muscle contractions drive embryo rotations. In turn, junctions between the lateral and dorso-ventral epidermis repeatedly oscillate between a folded, hypotensed state, and an extended, hypertensed state. Second, FRAP (Fluorescence Recovery After Photobleaching) analysis of an E-cadherin::GFP construct shows that muscle contractions stimulate E-cadherin turnover. Moreover, a mechano-chemical model backed by genetic tests suggests that E-cadherin trafficking modulates junction elongation due to lower line tension. Altogether, our results illustrate how muscle contractions fluidize epidermal adherens junctions, which, combined with anisotropic tension in the epidermis, drives their polarized extension.

developmental biology↗

bioRxiv2022

Glutamatergic projections from ventral hippocampus to nucleus accumbens cholinergic neurons are altered in a mouse model of depression

The cholinergic interneurons (ChATs) of the nucleus accumbens (NAc) have a critical role in the activity of this region, specifically in the context of major depressive disorder. To understand the circuitry regulating this behavior we sought to determine the areas that directly project to these cells/interneurons by utilizing the monosynaptic cell-specific tracing technique. Mapping showed monosynaptic projections that are exclusive to NAc ChATs. To determine if some of these projections are altered in a depression mouse model, we used mice that do not express the calcium binding protein p11 specifically in ChATs (ChAT-p11 cKO) and display a depressive-like phenotype. Our data demonstrated that while the overall projection areas remain similar between wild type and in ChAT-p11 cKO mice, the number of projections coming from the ventral hippocampus (vHIP) is significantly reduced in the ChAT-p11 cKO mice. Furthermore, using optogenetics and electrophysiology we showed that glutamatergic projections from vHIP to NAc ChATs are severely altered in mutant mice. These results show that specific alterations in the circuitry of the accumbal ChAT interneurons could play an important role in the regulation of depressive-like behavior, reward seeking behavior in addictions, or psychiatric symptoms in neurodegenerative diseases.

neuroscience↗

bioRxiv2019

The C. elegans plectin homologue VAB-10 acts as a hemidesmosome mechanosensor

Mechanical forces control many cellular processes by eliciting a mechanotransduction response in target cells. The initial steps of mechanotransduction at hemidesmosomes remain undefined in contrast to focal adhesions and adherens junctions. Here, we focus on the C. elegans plectin homolog VAB-10A, the only evolutionary conserved hemidesmosome component. In C. elegans, muscle contractions induce a mechanotransduction pathway in the epidermis through hemidesmosomes. We used CRISPR to precisely remove spectrin repeats (SR) or a partially hidden Src-homology-3 (SH3) domain within the VAB-10 plakin domain. Deleting the SH3 or SR8 domains in combination with mutations affecting mechanotransduction, or just part of SR5 shielding the SH3 domain induced embryonic elongation arrest because hemidesmosomes collapse. Notably, recruitment of GIT-1, the first mechanotransduction player, requires the SR5 domain and the hemidesmosome transmembrane receptor LET-805. Furthermore, Molecular Dynamics simulations confirmed that forces acting on VAB-10 can render the central SH3 domain, otherwise in contact with SR4, available for interaction. Collectively, our data strongly argue that the plakin domain plays a central role in mechanotransduction and raise the possibility that VAB-10/plectin might act as a mechanosensor.\n\nSummary statementCRISPR-derived deletions reveal the roles of three spectrin repeats and an atypical SH3 domain from the plakin domain of the VAB-10 hemidesmosome component in mechanotransduction during C. elegans morphogenesis

developmental biology↗