Browsing by Author "Vitorino, Marta"
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- Coronal brain atlas in stereotaxic coordinates of the African spiny mouse, acomys cahirinusPublication . Vitorino, Marta; S, Simão; Moreira, João B.; Nogueira‐Rodrigues, Joana; Silva, Joana A; Sofia Lourenço, Ana; Vitor Fernandes, Dr; Sousa, Monica M.; Tiscornia, Gustavo; Araújo, Inês MariaThe African spiny mouse (Acomys cahirinus) is an emerging model of mammalian epimorphic regeneration that has aroused the interest of the scientific community in the last decade. To date, studies on brain repair have been hindered by the lack of knowledge on the neuroanatomy of this species. Here, we present a coronal brain atlas in stereotaxic coordinates, which allows for three-dimensional identification and localization of the brain structures of this species. The brain of 12-week-old spiny mice was mapped in stereotaxic coordinates using cresyl violet-stained brain sections obtained from coronal cryosectioning of the brain after transcardial perfusion with fixative. The atlas is presented in 42 plates representing sections spaced 240 mu m apart. Stereotaxic coordinates were validated using both a model of Parkinsonian lesion of the striatum with 6-hydroxydopamine and labeling of the corticospinal tract in the spiny mouse spinal cord using AAV1/2-GFP intracortical injections. This work presents a new tool in A. cahirinus neurobiology and opens new avenues of research for the investigation of the regenerative ability of A. cahirinus in models of brain disorders.
- Developmental expression of Shisa-2 in Xenopus laevisPublication . Silva, Ana-Cristina; Filipe, Mario; Vitorino, Marta; Steinbeisser, Herbert; Belo, José A.Shisa is an antagonist of Wnt and FGF signaling, that functions cell autonomously in the endoplasmic reticulum (ER) to inhibit the post-translational maturation of Wnt and FGF receptors. In this paper we report the isolation of a second Xenopus shisa gene (Xshisa-2). Xenopus Shisa-2shows 30.7% identity to Xshisa. RT-PCR analysis indicated that Xshisa-2 mRNA is present throughout early development and shows an increased expression during neurula and tailbud stages. At neurula stages Xenopus shisa-2 is initially expressed in the presomitic paraxial mesoderm and later in the developing somites. The expression profiles and pattern of Xshisa and Xshisa-2 differ significantly. During gastrulation only Xshisa mRNA is present in the Spemann-Mangold organizer and later on becomes restricted to the neuroectoderm and the prechordal plate.
- Generating asymmetries in the early vertebrate embryo: the role of the Cerberus-like familyPublication . Belo, José A.; Silva, Ana C.; Borges, Ana; Filipe, Mário; Bento, Margaret; Gonçalves, Lisa; Vitorino, Marta; Salgueiro, Ana Marisa; Texeira, Vera; Tavares, Ana T.; Marques, SaraOne fundamental aspect of vertebrate embryonic development is the formation of the body plan. For this process, asymmetries have to be generated during early stages of development along the three main body axes: Anterior-Posterior, Dorso-Ventral and Left-Right. We have been studying the role of a novel class of molecules,the Cerberus/Dan gene family. These are dedicated secreted antagonists of three major signaling pathways: Nodal, BMP and Wnt. Our studies contribute to the current view that the fine tuning of signaling is controlled by a set of inhibitory molecules rather than by activators. In this context, the Cerberus-like molecules emerge as key players in the regulation and generation of asymmetries in the early vertebrate embryo.
- Matrisomal components involved in regenerative wound healing in axolotl and acomys: implications for biomaterial developmentPublication . Avila-Martinez, Nancy; Gansevoort, Merel; Verbakel, Juul; Jayaprakash, Haarshaadri; Araujo, Ines; Vitorino, Marta; Tiscornia, Gustavo; van Kuppevelt, Toin H.; Daamen, Willeke F.Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.
- mef2ca and mef2cb Double mutant Zebrafish show altered craniofacial phenotype and motor behaviourPublication . Adrião, Andreia; Mariano, Sara; Mariano, José; Gavaia, Paulo; Cancela, M. Leonor; Vitorino, Marta; Conceição, NatérciaThe transcription factor MEF2C is crucial in neuronal, cardiac, bone and cartilage molecular processes, as well as for craniofacial development. MEF2C was associated with the human disease MRD20, whose patients show abnormal neuronal and craniofacial development. Zebrafish mef2ca;mef2cb double mutants were analysed for abnormalities in craniofacial and behaviour development through phenotypic analysis. Quantitative PCR was performed to investigate the expression levels of neuronal marker genes in mutant larvae. The motor behaviour was analysed by the swimming activity of 6 dpf larvae. We found that mef2ca;mef2cb double mutants display several abnormal phenotypes during early development, including those already described in zebrafish carrying mutations in each paralog, but also (i) a severe craniofacial phenotype (comprising both cartilaginous and dermal bone structures), (ii) developmental arrest due to the disruption of cardiac oedema and (iii) clear alterations in behaviour. We demonstrate that the defects observed in zebrafish mef2ca;mef2cb double mutants are similar to those previously described in MEF2C-null mice and MRD20 patients, confirming the usefulness of these mutant lines as a model for studies concerning MRD20 disease, the identification of new therapeutic targets and screening for possible rescue strategies.
- Rewired glycosylation activity promotes scarless regeneration and functional recovery in spiny mice after complete spinal cord transectionPublication . Nogueira-Rodrigues, Joana; Leite, Sérgio C.; Pinto-Costa, Rita; Sousa, Sara C.; Luz, Liliana L.; Sintra, Maria A.; Oliveira, Raquel; Monteiro, Ana C.; Pinheiro, Gonçalo; Vitorino, Marta; Silva, Joana A.; S, Simão; Vitor Fernandes, Dr; Provazník, Jan; Benes, Vladimir; Cruz, Célia D.; Safronov, Boris V.; Magalhães, Ana; Reis, Celso A.; Vieira, Jorge; Vieira, Cristina P.; Tiscórnia, Gustavo; Araujo, Ines; Sousa, Mónica M.Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies beta 3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.
- Study of Xenopus orthologs of novel genes expressed in the mouse AVEPublication . Becker, Jorg D.; Steinbeisser, Herbert; Belo, A.; Silva, Ana C.; Vitorino, Marta; Filipa, Mário; Marques, Sara
- Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling PathwayPublication . Vitorino, Marta; Silva, Ana Cristina; Inacio, Jose Manuel; Ramalho, Jose Silva; Gur, Michal; Fainsod, Abraham; Steinbeisser, Herbert; Belo, José A.Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway.
- Zebrafish: an interesting model to study CDKL5 deficiency disorderPublication . Varela, Tatiana; Varela, Débora; Vitorino, Marta; Conceição, Natércia; Cancela, M. Leonor; Martins, GilCDKL5 deficiency disorder is a rare X-linked condition that results in early onset of impairedmotor and cognitive skills such as motor rigidity, stereotypical hand movements and deficient language acquisition aswell as recurrent seizures. It is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, which encodes a serine/threonine kinase involved in important neuronal processes such as cell signaling and neuron morphogenesis.