Biology subjects

Oldani, A.

Publications and source records attributed to Oldani, A..

4 recordsLinked to original sources

bioRxiv2021

Decellularized Normal and Tumor Scaffolds for Cancer Organoid Cultures as a Model of Colorectal Peritoneal Metastases

Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. SignificanceEvidence of the value of ex vivo 3D models obtained by combining patient-derived extracellular matrices depleted of cellular components and organoids to mimic the metastatic niche, to be used as a tool to develop new therapeutic strategies in a biologically relevant context, to personalize treatments and increase their efficacy.

cancer biology↗

bioRxiv2020

The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Specialised ribonucleoprotein (RNP) granules are a hallmark of germ cells. Among their main function is the spatial and temporal modulation of the activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis. Loss of Hecw activity results in the formation of enlarged granules that transition from a liquid to a gel-like state. At the molecular level, Hecw depletion leads to reduced ubiquitination and activity of the translational repressor Fmrp, resulting in premature Orb expression/recruitment in nurse cells. In addition to defective oogenesis, flies lacking Hecw show neurodegenerative traits with premature aging and climbing defects due to neuronal loss that are linked to RNPs condensation. Our findings reveal an unprecedented function of ubiquitin in modulating RNP fluidity and activity.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2019

IRSp53 shapes the plasma membrane and controls polarized transport at the nascent lumen during epithelial morphogenesis

Establishment of apical-basal cell polarity is necessary for generation of luminal and tubular structures during epithelial morphogenesis. Molecules acting at the membrane/ actin interface are expected to be crucial in governing these processes. Here, we show that the I-BAR-containing IRSp53 protein is restricted to the luminal side of epithelial cells of various glandular organs, and is specifically enriched in renal tubules in human, mice, and zebrafish. Using three-dimensional cultures of renal MDCK and intestinal Caco-2 cysts, we show that IRSp53 is recruited early after the first cell division along the forming apical lumen, and is essential for formation of a single lumen and for positioning of the polarity determinants aPKC and podocalyxin. Molecularly, IRSp53 directly binds to and controls localization of the inactive form of the small GTPase RAB35, a tethering factor for apical determinants. The interaction of IRSp53 with the actin capping protein EPS8 is critical for restricting IRSp53 localization. Correlative light and electron microscopy shows that IRSp53 loss perturbs the shape and continuity of the opposing apical membrane during the initial phase of lumenogenesis, which leads to preservation of multiple cytoplasmic bridges that interrupt the continuity of the nascent lumen. At the organism level, genetic removal of IRSp53 results in abnormal renal tubulogenesis, with defects in tubular polarity and architectural organization in both IRSp53 zebrafish mutant lines and IRSp53-KO murine models. Thus, IRSp53 acts as a platform for spatiotemporal regulation of assembly of the multi-protein complexes that shape the luminal membrane during the early steps of epithelial lumen morphogenesis.

developmental biology↗

bioRxiv2019

From injury to full repair: nerve regeneration and functional recovery in the common octopus, Octopus vulgaris

Spontaneous nerve regeneration in cephalopod molluscs occurs in a relative short time after injury, achieving functional recovery of the lost capacities. In particular, transection of the pallial nerve in the common octopus (Octopus vulgaris) determines loss and subsequent restoring of two functions fundamental for survival, i.e. breathing and skin patterning, the latter involved in communication between animals and concealing. The phenomena occurring after lesion have been investigated in a series of previous studies, but a complete analysis of the changes occurring at the level of the axons and the effects on animals appearance during the whole regenerative process is still missing. Our goal is to determine the course of events following injury. Our goal is to determine the course of events following injury, from impairment to full recovery.\n\nWe observed nerve regeneration, end-target re-innervation and functional reconnections between central brain and periphery, using the contralateral nerve in the same animal as internal control. The final architecture of the regenerated nervous tissue does not mirror the original structure, however functionality returns to match the phenotype of an intact octopus, and with no visible impact on the behaviour of the animal. This provides exceptional value to these findings for future studies.\n\nSummary statementHere we report events occurring after interruption of the peripheral neural circuitry in Octopus vulgaris, from the dramatic loss of normal functioning to full recovery.

neuroscience↗