Anatomia além do laboratório: a história de uma liga acadêmica de anatomia geral / Anatomy beyond the laboratory: the history of an academic league of general anatomy

Introdução: Ligas acadêmicas buscam ampliar a formação médica dos acadêmicos. Representam entidades com autonomia perante a faculdade, desenvolvidas por discentes e supervisionadas por docentes, apoiadas no tripé ensino, pesquisa e extensão. Objetivos: Relatar a experiência de um grupo de estudos em anatomia; descrever a fundação de uma liga acadêmica, elucidando os diversos aspectos que envolveram esse processo, a experiência dos membros, os impasses e os benefícios; ressaltar os trabalhos, principalmente no âmbito científico, desenvolvidos desde sua fundação, em 2019, até 2022; ampliar as informações na literatura sobre o trabalho desenvolvido pelas ligas e exemplificar atividades que tiveram êxito. Método: Estudo descritivo. Em 2018, alunos do primeiro ano do curso de medicina criaram um grupo de estudos de anatomia, buscando aprimoramento técnico-científico. Com a ajuda do docente da disciplina e, em 2019, fundaram a Liga Acadêmica de Anatomia Geral, no Centro Universitário Padre Albino. Resultados: A liga tem possibilitado uma conexão próxima entre os estudantes e a comunidade local, acadêmica e científica. Tornou-se referência na faculdade a partir do suporte à iniciação científica envolvendo alunos desde o primeiro semestre da graduação, com a realização de 11 projetos de pesquisa até agosto de 2022. Conclusão: Ligas acadêmicas de anatomia permitem a intersecção de diversas especialidades médicas, promovendo a especialização precoce e o aperfeiçoando do conhecimento generalista

Introduction: Academic leagues seek to expand the medical training of academics. They represent entities with autonomy before the faculty, developed by students and supervised by teachers, based on the tripod of teaching, research and extension. Objectives: Report the experience of an anatomy study group; describe the founding of an academic league, elucidating the various aspects that involved this process, the members' experience, the impasses and the benefits; highlight the work, mainly in the scientific field, developed since its foundation, in 2019, until 2022; expand information in the literature about the work carried out by the leagues and exemplify activities that were successful. Method: Descriptive study. In 2018, first-year medical students created an anatomy study group, seeking technical-scientific improvement. With the help of the subject teacher and, in 2019, they founded the General Anatomy Academic League, at the Padre Albino University Center. Results: The league has enabled a close connection between students and the local academic and scientific community. It became a reference in the faculty by supporting scientific initiation involving students from the first semester of graduation, with the completion of 11 research projects until August 2022. Conclusion: Anatomy academic leagues allow the intersection of different medical specialties, promoting early specialization and the improvement of generalist knowledge.

Emerging concepts on the mechanical interplay between migrating cells and microenvironment in vivo.

During embryogenesis, tissues develop into elaborate collectives through a myriad of active mechanisms, with cell migration being one of the most common. As cells migrate, they squeeze through crowded microenvironments to reach the positions where they ultimately execute their function. Much of our knowledge of cell migration has been based on cells' ability to navigate in vitro and how cells respond to the mechanical properties of the extracellular matrix (ECM). These simplified and largely passive surroundings contrast with the complexity of the tissue environments in vivo, where different cells and ECM make up the milieu cells migrate in. Due to this complexity, comparatively little is known about how the physical interactions between migrating cells and their tissue environment instruct cell movement in vivo. Work in different model organisms has been instrumental in addressing this question. Here, we explore various examples of cell migration in vivo and describe how the physical interplay between migrating cells and the neighboring microenvironment controls cell behavior. Understanding this mechanical cooperation in vivo will provide key insights into organ development, regeneration, and disease.

Multiciliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo.

During embryonic development, regeneration, and homeostasis, cells have to migrate and physically integrate into the target tissues where they ultimately execute their function. While much is known about the biochemical pathways driving cell migration in vivo, we are only beginning to understand the mechanical interplay between migrating cells and their surrounding tissue. Here, we reveal that multiciliated cell precursors in the Xenopus embryo use filopodia to pull at the vertices of the overlying epithelial sheet. This pulling is effectively used to sense vertex stiffness and identify the preferred positions for cell integration into the tissue. Notably, we find that pulling forces equip multiciliated cells with the ability to remodel the epithelial junctions of the neighboring cells, enabling them to generate a permissive environment that facilitates integration. Our findings reveal the intricate physical crosstalk at the cell-tissue interface and uncover previously unknown functions for mechanical forces in orchestrating cell integration.

Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC.

Apical-basal polarity underpins the formation of epithelial barriers that are crucial for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. Lgl plays a role as an aPKC inhibitor, but it remains unclear whether Lgl also forms complexes with Dlg or Scrib. Using fluorescence recovery after photobleaching, we show that Lgl does not form immobile complexes at the lateral domain of Drosophila follicle cells. Optogenetic depletion of plasma membrane PIP2 or dlg mutants accelerate Lgl cortical dynamics. However, Dlg and Scrib are required only for Lgl localization and dynamic behavior in the presence of aPKC function. Furthermore, light-induced oligomerization of basolateral proteins indicates that Lgl is not part of the Scrib-Dlg complex in the follicular epithelium. Thus, Scrib and Dlg are necessary to repress aPKC activity in the lateral domain but do not provide cortical binding sites for Lgl. Our work therefore highlights that Lgl does not act in a complex but in parallel with Scrib-Dlg to antagonize apical determinants.

PP1-Mediated Dephosphorylation of Lgl Controls Apical-basal Polarity.

Apical-basal polarity is a common trait that underlies epithelial function. Although the asymmetric distribution of cortical polarity proteins works in a functioning equilibrium, it also retains plasticity to accommodate cell division, during which the basolateral determinant Lgl is released from the cortex. Here, we investigated how Lgl restores its cortical localization to maintain the integrity of dividing epithelia. We show that cytoplasmic Lgl is reloaded to the cortex at mitotic exit in Drosophila epithelia. Lgl cortical localization depends on protein phosphatase 1, which dephosphorylates Lgl on the serines phosphorylated by aPKC and Aurora A kinases through a mechanism that relies on the regulatory subunit Sds22 and a PP1-interacting RVxF motif of Lgl. This mechanism maintains epithelial polarity and is of particular importance at mitotic exit to couple Lgl cortical reloading with the polarization of the apical domain. Hence, PP1-mediated dephosphorylation of Lgl preserves the apical-basal organization of proliferative epithelia.

Aurora A triggers Lgl cortical release during symmetric division to control planar spindle orientation.

Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.

A transient increase in total head phosphotyrosine levels is observed upon the emergence of Aedes aegypti from the pupal stage.

Phosphorylation and dephosphorylation of protein tyrosine residues constitutes a major biochemical regulatory mechanism for the cell. We report a transient increase in the total tyrosine phosphorylation of the Aedes aegypti head during the first days after emergence from the pupal stage. This correlates with an initial reduction in total head protein tyrosine phosphatase (PTP) activity. Similarly, phosphotyrosine (pTyr)-containing bands are seen in extracts prepared from both male and female heads and are spread among a variety of structures including the antennae, proboscis and the maxillary palps combined with the proboscis. Also, mosquitoes treated with sodium orthovanadate, a classical PTP inhibitor, show reduced blood-feeding activity and higher head tyrosine phosphorylation levels. These results suggest that pTyr-mediated signalling pathways may play a role in the initial days following the emergence of the adult mosquito from the pupal stage.

A transient increase in total head phosphotyrosine levels is observed upon the emergence of Aedes aegypti from the pupal stage

Phosphorylation and dephosphorylation of protein tyrosine residues constitutes a major biochemical regulatory mechanism for the cell. We report a transient increase in the total tyrosine phosphorylation of the Aedes aegypti head during the first days after emergence from the pupal stage. This correlates with an initial reduction in total head protein tyrosine phosphatase (PTP) activity. Similarly, phosphotyrosine (pTyr)-containing bands are seen in extracts prepared from both male and female heads and are spread among a variety of structures including the antennae, proboscis and the maxillary palps combined with the proboscis. Also, mosquitoes treated with sodium orthovanadate, a classical PTP inhibitor, show reduced blood-feeding activity and higher head tyrosine phosphorylation levels. These results suggest that pTyr-mediated signalling pathways may play a role in the initial days following the emergence of the adult mosquito from the pupal stage.