PM- Artigos
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- Epha1 is a cell-surface marker for the neuromesodermal competent populationPublication . de Lemos, Luisa; Dias, André; Nóvoa, Ana; Mallo, Moisés
- Isolated Incudostapedial Cholesteatomas: Unique Radiologic and Surgical FeaturesPublication . MacDonald, Bridget; Bommakanti, Krishna; Mallo, Moises; Carvalho, Daniela
- Of Necks, Trunks and Tails: Axial Skeletal Diversity among VertebratesPublication . Mallo, Moisés
- Three and Four-Dimensional Visualization and Analysis Approaches to Study Vertebrate Axial Elongation and SegmentationPublication . Dias, André; Martins, Gabriel G.; Lopes, Alexandre; Mallo, Moisés
- Patterning and Morphogenesis From Cells to Organisms: Progress, Common Principles and New ChallengesPublication . Goryachev, Andrew B.; Mallo, Moisés
- A Tgfbr1/Snai1-dependent developmental module at the core of vertebrate axial elongationPublication . Dias, André; Lozovska, Anastasiia; Wymeersch, Filip J; Nóvoa, Ana; Binagui-Casas, Anahi; Sobral, Daniel; Martins, Gabriel G; Wilson, Valerie; Mallo, Moises
- The vertebrate tail: a gene playground for evolutionPublication . Mallo, MoisésThe tail of all vertebrates, regardless of size and anatomical detail, derive from a post-anal extension of the embryo known as the tail bud. Formation, growth and differentiation of this structure are closely associated with the activity of a group of cells that derive from the axial progenitors that build the spinal cord and the muscle-skeletal case of the trunk. Gdf11 activity switches the development of these progenitors from a trunk to a tail bud mode by changing the regulatory network that controls their growth and differentiation potential. Recent work in the mouse indicates that the tail bud regulatory network relies on the interconnected activities of the Lin28/let-7 axis and the Hox13 genes. As this network is likely to be conserved in other mammals, it is possible that the final length and anatomical composition of the adult tail result from the balance between the progenitor-promoting and -repressing activities provided by those genes. This balance might also determine the functional characteristics of the adult tail. Particularly relevant is its regeneration potential, intimately linked to the spinal cord. In mammals, known for their complete inability to regenerate the tail, the spinal cord is removed from the embryonic tail at late stages of development through a Hox13-dependent mechanism. In contrast, the tail of salamanders and lizards keep a functional spinal cord that actively guides the tail's regeneration process. I will argue that the distinct molecular networks controlling tail bud development provided a collection of readily accessible gene networks that were co-opted and combined during evolution either to end the active life of those progenitors or to make them generate the wide diversity of tail shapes and sizes observed among vertebrates.
- Two CRISPR/Cas9-mediated methods for targeting complex insertions, deletions, or replacements in mousePublication . Pineault, Kyriel M.; Novoa, Ana; Lozovska, Anastasiia; Wellik, Deneen M.; Mallo, MoisesGenetically modified model organisms are valuable tools for probing gene function, dissecting complex signaling networks, studying human disease, and more. CRISPR/Cas9 technology has significantly democratized and reduced the time and cost of generating genetically modified models to the point that small gene edits are now routinely and efficiently generated in as little as two months. However, generation of larger and more sophisticated gene-modifications continues to be inefficient. Alternative ways to provide the replacement DNA sequence, method of Cas9 delivery, and tethering the template sequence to Cas9 or the guide RNA (gRNA) have all been tested in an effort to maximize homology-directed repair for precise modification of the genome. We present two CRISPR/Cas9 methods that have been used to successfully generate large and complex gene-edits in mouse. In the first method, the Cas9 enzyme is used in conjunction with two sgRNAs and a long single-stranded DNA (lssDNA) template prepared by an alternative protocol. The second method utilizes a tethering approach to couple a biotinylated, double-stranded DNA (dsDNA) template to a Cas9-streptavidin fusion protein. •Alternative method for generating long, single-stranded DNA templates for CRISPR/Cas9 editing.•Demonstration that using two sgRNAs with Cas9-streptavidin/biotinylated-dsDNA is feasible for large DNA modifications.
- Reassessing the Role of Hox Genes during Vertebrate Development and EvolutionPublication . Mallo, MoisésSince their discovery Hox genes have been at the core of the established models explaining the development and evolution of the vertebrate body plan as well as its paired appendages. Recent work brought new light to their role in the patterning processes along the main body axis. These studies show that Hox genes do not control the basic layout of the vertebrate body plan but carry out region-specific patterning instructions loaded on the derivatives of axial progenitors by Hox-independent processes. Furthermore, the finding that Hox clusters are embedded in functional chromatin domains, which critically impacts their expression, has significantly altered our understanding of the mechanisms of Hox gene regulation. This new conceptual framework has broadened our understanding of both limb development and the evolution of vertebrate paired appendages.
- Deconstructing the molecular mechanisms shaping the vertebrate body planPublication . Aires, Rita; Dias, André; Mallo, MoisésThe large display of body shapes and sizes observed among vertebrates ultimately represent variations of a common basic body plan. This likely results from the use of homologous developmental schemes, just differentially tinkered both in amplitude and timing by natural selection. In this review, we will revisit, discuss and combine old ideas with new concepts to update our view on how the vertebrate body is built. Recent advances, particularly at the molecular level, will guide our deconstruction of the individual developmental modules that sequentially produce head, neck, trunk and tail structures, and the transitions between them.
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