Browsing by Author "Concha, Miguel L."

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    A computational framework for testing hypotheses of the minimal mechanical requirements for cell aggregation using early annual killifish embryogenesis as a model
    (FRONTIERS MEDIA SA, 2023) Montenegro-Rojas, Ignacio; Yanez, Guillermo; Skog, Emily; Guerrero-Calvo, Oscar; Andaur-Lobos, Martin; Dolfi, Luca; Cellerino, Alessandro; Cerda, Mauricio; Concha, Miguel L.; Bertocchi, Cristina; Rojas, Nicolas O.; Ravasio, Andrea; Rudge, Timothy J.
    Introduction: Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate de novo cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface. Therefore, the first stage of embryogenesis requires the congregation of embryonic cells at one pole of the egg to form a single aggregate that later gives rise to the embryo proper. This unique process presents an opportunity to dissect the self-organizing principles involved in early organization of embryonic stem cells. Indeed, the physical and biological processes required to form the aggregate of embryonic cells are currently unknown., Methods: Here, we developed an in silico, agent-based biophysical model that allows testing how cell-specific and environmental properties could determine the aggregation dynamics of early Killifish embryogenesis. In a forward engineering approach, we then proceeded to test two hypotheses for cell aggregation (cell-autonomous and a simple taxis model) as a proof of concept of modeling feasibility. In a first approach (cell autonomous system), we considered how intrinsic biophysical properties of the cells such as motility, polarity, density, and the interplay between cell adhesion and contact inhibition of locomotion drive cell aggregation into self-organized clusters. Second, we included guidance of cell migration through a simple taxis mechanism to resemble the activity of an organizing center found in several developmental models., Results: Our numerical simulations showed that random migration combined with low cell-cell adhesion is sufficient to maintain cells in dispersion and that aggregation can indeed arise spontaneously under a limited set of conditions, but, without environmental guidance, the dynamics and resulting structures do not recapitulate in vivo observations., Discussion: Thus, an environmental guidance cue seems to be required for correct execution of early aggregation in early killifish development. However, the nature of this cue (e.g., chemical or mechanical) can only be determined experimentally. Our model provides a predictive tool that could be used to better characterize the process and, importantly, to design informed experimental strategies.
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    Chronic stress decreases the expression of sympathetic markers in the pineal gland and increases plasma melatonin concentration in rats
    (WILEY, 2006) Dagnino Subiabre, Alexies; Orellana, Juan A.; Carmona Fontaine, Carlos; Montiel, Juan; Diaz Veliz, Gabriela; Seron Ferre, Maria; Wyneken, Ursula; Concha, Miguel L.; Aboitiz, Francisco
    Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and alpha-tubulin, while the same treatment did not affect the expression of the non-specific sympathetic markers Erk1 and Erk2, and glyceraldehyde-3-phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.
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    Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth
    (2013) Colombo, Alicia; Palma, Karina; Armijo, Lorena; Mione, Marina; Signore, Iskra A.; Morales, Camila; Guerrero, Néstor; Meynard, Margarita M.; Pérez, Ramón; Suazo, José; Marcelain, Katherine; Briones, Luis; Häertel, Steffen; Wilson, Stephen W.; Concha, Miguel L.
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    Expression of RPRM/rprm in the olfactory system of embryonic zebrafish (Danio rerio)
    (2018) Stanic, Karen; Quiroz Vallverdu, Alonso Ingmar; Lemus, Carmen G.; Wichmann Pérez, Ignacio Alberto; Corvalán R., Alejandro; Owen, Gareth Ivor; Opazo, Juan C.; Concha, Miguel L.; Amigo Donoso, Julio
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    Organization of the Catecholaminergic System in the Short-Lived Fish Nothobranchius furzeri
    (2021) Borgonovo, Janina; Ahumada-Galleguillos, Patricio; Onate-Ponce, Alejandro; Allende-Castro, Camilo; Henny, Pablo; Concha, Miguel L.
    The catecholaminergic system has received much attention based on its regulatory role in a wide range of brain functions and its relevance in aging and neurodegenerative diseases. In the present study, we analyzed the neuroanatomical distribution of catecholaminergic neurons based on tyrosine hydroxylase (TH) immunoreactivity in the brain of adult Nothobranchius furzeri. In the telencephalon, numerous TH+ neurons were observed in the olfactory bulbs and the ventral telencephalic area, arranged as strips extending through the rostrocaudal axis. We found the largest TH+ groups in the diencephalon at the preoptic region level, the ventral thalamus, the pretectal region, the posterior tuberculum, and the caudal hypothalamus. In the dorsal mesencephalic tegmentum, we identified a particular catecholaminergic group. The rostral rhombencephalon housed TH+ cells in the locus coeruleus and the medulla oblongata, distributing in a region dorsal to the inferior reticular formation, the vagal lobe, and the area postrema. Finally, scattered TH+ neurons were present in the ventral spinal cord and the retina. From a comparative perspective, the overall organization of catecholaminergic neurons is consistent with the general pattern reported for other teleosts. However, N. furzeri shows some particular features, including the presence of catecholaminergic cells in the midbrain. This work provides a detailed neuroanatomical map of the catecholaminergic system of N. furzeri, a powerful aging model, also contributing to the phylogenetic understanding of one of the most ancient neurochemical systems.
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    The Reprimo gene family member, reprimo-like (rprml), is required for blood development in embryonic zebrafish
    (2019) Stanic, Karen; Reig, German; Figueroa, Ricardo J.; Retamal, PedroA.; Wichmann Pérez, Ignacio Alberto; Opazo, JuanC.; Owen, Gareth Ivor; Corvalán R., Alejandro; Concha, Miguel L.; Amigo, Julio
    The Reprimo gene family comprises a group of sing le-exon genes for which their physiological function remains poorly understood. Heretofore, mammalian Reprimo (RPRM) has been described as a putative p53-dependent tumor suppressor gene that functions at the G2/M cell cycle checkpoint. Another family member, Reprimo-like (RPRML), has not yet an established role in physiology or pathology. Importantly, RPRML expression pattern is conserved between zebrafish and human species. Here, using CRISPR-Cas9 and antisense morpholino oligonucleotides, we disrupt the expression of rprml in zebrafish and demonstrate that its loss leads to impaired definitive hematopoiesis. The formation of hemangioblasts and the primitive wave of hematopoiesis occur normally in absence of rprml Later in development there is a significant reduction in erythroid-myeloid precursors (EMP) at the posterior blood island (PBI) and a significant decline of definitive hematopoietic stem/progenitor cells (HSPCs). Furthermore, loss of rprml also increases the activity of caspase-3 in endothelial cells within the caudal hematopoietic tissue (CHT), the first perivascular niche where HSPCs reside during zebrafish embryonic development. Herein, we report an essential role for rprml during hematovascular development in zebrafish embryos, specifically during the definitive waves of hematopoiesis, indicating for the first time a physiological role for the rprml gene.