Browsing by Author "Contreras, Esteban G."

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    A role for Lin-28 in growth and metamorphosis in Drosophila melanogaster
    (2018) Gonzalez-Itier, Sergio; Contreras, Esteban G.; Larraín Correa, Juan Agustín; Glavic, Alvaro; Faunes Quinteros, Fernando Emerson
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    Early requirement of Hyaluronan for tail regeneration in Xenopus tadpoles
    (COMPANY OF BIOLOGISTS LTD, 2009) Contreras, Esteban G.; Gaete, Marcia; Sanchez, Natalia; Carrasco, Hector; Larrain, Juan
    Tail regeneration in Xenopus tadpoles is a favorable model system to understand the molecular and cellular basis of tissue regeneration. Although turnover of the extracellular matrix (ECM) is a key event during tissue injury and repair, no functional studies to evaluate its role in appendage regeneration have been performed. Studying the role of Hyaluronan (HA), an ECM component, is particularly attractive because it can activate intracellular signaling cascades after tissue injury. Here we studied the function of HA and components of the HA pathway in Xenopus tadpole tail regeneration. We found that transcripts for components of this pathway, including Hyaluronan synthase2 (HAS2), Hyaluronidase2 and its receptors CD44 and RHAMM, were transiently upregulated in the regenerative bud after tail amputation. Concomitantly, an increase in HA levels was observed. Functional experiments using 4-methylumbelliferone, a specific HAS inhibitor that blocked the increase in HA levels after tail amputation, and transgenesis demonstrated that the HA pathway is required during the early phases of tail regeneration. Proper levels of HA are required to sustain proliferation of mesenchymal cells in the regenerative bud. Pharmacological and genetic inhibition of GSK3 beta was sufficient to rescue proliferation and tail regeneration when HA synthesis was blocked, suggesting that GSK3 beta is downstream of the HA pathway. We have demonstrated that HA is an early component of the regenerative pathway and is required for cell proliferation during the early phases of Xenopus tail regeneration. In addition, a crosstalk between HA and GSK3 beta signaling during tail regeneration was demonstrated.
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    Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells
    (2012) Gaete Carrasco, Marcia; Valle Muñoz Videla, Rosana del.; Sánchez, Natalia.; Tampe, Ricardo.; Moreno Concha, Mauricio; Contreras, Esteban G.; Lee Liu, Dasfne.; Larraín Correa, Juan Agustín
    Abstract Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection.