Browsing by Issue Date, starting with "2025-01-29"
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- Assessing the importance of deltaC mRNA 3’utr for zebrafish somitogenesisPublication . Rodrigues, Leonardo Abraão da Silva; Andrade, Raquel P.; Carraco, GilSomitogenesis is a critical process in early vertebrate development, leading to the periodic formation of somites from the presomitic mesoderm (PSM) along the rostral-caudal axis during body elongation. These somites, which serve as embryonic precursors to the axial skeleton, are crucial for the proper development of vertebrae and other segmented structures. While the periodicity of somite formation can vary significantly between species, it remains highly constant within each species. This periodicity is driven by the embryo clock (EC), an intrinsic mechanism in PSM cells that relies on oscillations of gene expression, regulated through negative feedback loops, requiring short-lived mRNA transcripts. The stability of these transcripts is influenced by regulatory regions (RR) within the mRNA 3’ Untranslated Region (3’UTR). Proper somite formation requires synchronization between PSM cells, facilitated by Notch-Delta signaling, which coordinates cellular division and differentiation. This work investigated the role of the 3’UTR of the zebrafish deltaC clock gene in somite formation periodicity. Various zebrafish mutant lines were generated using CRISPR/Cas9. A previously generated mutant line (RR2) was characterized, assessing somite number, size, periodicity of formation, as well as the expression of EC genes. The comparison between the RR2 mutant and wildtype embryos showed no differences in somite size or number. Also, deltaC and her7 clock gene expression were unaltered. However, the RR2 mutant showed a slight decrease in the periodicity of somite formation. In conclusion, this work describes new animal model systems to study the embryo clock and provided new data on the importance of deltaC mRNA 3’UTR for somite formation.
- Unraveling the role of extracellular vesicles in spinocerebellar ataxia type 2 progressionPublication . Martins, Jéssica Alexandra Sousa; Nóbrega, ClévioSpinocerebellar ataxia type 2 (SCA2) is a neurodegenerative polyglutamine disorder caused by an aberrant expansion of the adenine-cytosine-guanine (CAG) trinucleotide in the coding region of the ATXN2 gene. This mutation results in an abnormally expanded polyglutamine tract in ataxin-2, the protein product of this gene, which promotes aggregation and the formation of inclusion bodies within the brains of SCA2 patients. Clinically, SCA2 presents as a multisystem disorder with both motor and non-motor symptoms. Neurodegeneration primarily affects the cerebellum and its neuronal pathways, leading to gait ataxia, which is the most prominent clinical feature of SCA2 and a hallmark of all SCAs. Although only certain neuroanatomical regions are initially affected, degeneration appears to spread to other brain regions as the disease progresses. In recent years, substantial evidence has suggested that extracellular vesicles (EVs) may mediate the neuron-to-neuron transfer of aggregation-prone proteins implicated in several neurodegenerative diseases. This mechanism has been shown to induce toxicity in healthy recipient cells, potentially contributing to disease propagation. Based on this evidence, the present study aimed to determine whether ataxin-2-loaded exosomes, a specific EV subtype, can mediate the spread of mutant ataxin-2 and induce a SCA2-like phenotype in vivo. To this end, we conducted comprehensive motor behavioral and neuropathological analyses. Our findings show that mice injected with ataxin-2-loaded exosomes exhibited gait and posture alterations consistent with progressive motor impairment and an ataxic phenotype, alongside signs of neuroinflammation, such as astrogliosis, early Purkinje cell degeneration, and ataxin-2 aggregate-like formation. This study provides new insights into the role of EVs in SCA2 progression and suggests that ataxin-2-loaded exosomes can facilitate the spread of mutant ataxin-2, contributing to SCA2 pathology in vivo.