Extension and patterning of the vertebrate body

Dissertation presented to obrain the Ph.D degree in Biology. Developmental BiologyVertebrates exhibit an enormous diversity in body shapes. Despite this variability, they all develop by a common principle, in which new tissue is continuously added at the posterior embryonic end during development. Axial extension requires a tight balance between the maintenance of axial progenitors in an undifferentiated state and the production of cells fated to generate different body structures. Concurrently, newly formed tissues are endowed with patterning information that coordinates their differentiation.(...

Compartment-dependent activities of Wnt3a/β-catenin signaling during vertebrate axial extension

Extension of the vertebrate body results from the concerted activity of many signals in the posterior embryonic end. Among them, Wnt3a has been shown to play relevant roles in the regulation of axial progenitor activity, mesoderm formation and somitogenesis. However, its impact on axial growth remains to be fully understood. Using a transgenic approach in the mouse, we found that the effect of Wnt3a signaling varies depending on the target tissue. High levels of Wnt3a in the epiblast prevented formation of neural tissues, but did not impair axial progenitors from producing different mesodermal lineages. These mesodermal tissues maintained a remarkable degree of organization, even within a severely malformed embryo. However, from the cells that failed to take a neural fate, only those that left the epithelial layer of the epiblast activated a mesodermal program. The remaining tissue accumulated as a folded epithelium that kept some epiblast-like characteristics. Together with previously published observations, our results suggest a dose-dependent role for Wnt3a in regulating the balance between renewal and selection of differentiation fates of axial progenitors in the epiblast. In the paraxial mesoderm, appropriate regulation of Wnt/β-catenin signaling was required not only for somitogenesis, but also for providing proper anterior-posterior polarity to the somites. Both processes seem to rely on mechanisms with different requirements for feedback modulation of Wnt/β-catenin signaling, once segmentation occurred in the presence of high levels of Wnt3a in the presomitic mesoderm, but not after permanent expression of a constitutively active form of β-catenin. Together, our findings suggest that Wnt3a/β-catenin signaling plays sequential roles during posterior extension, which are strongly dependent on the target tissue. This provides an additional example of how much the functional output of signaling systems depends on the competence of the responding cells.Fundação para a Ciência e a Tecnologia: (PTDC/BIA-BCM/110638/2009, PTDC/SAU-BID/110640/2009, SFRH/BD/33562/2008, SFRH/BD/51876/2012)

Switching Axial Progenitors from Producing Trunk to Tail Tissues in Vertebrate Embryos

The vertebrate body is made by progressive addition of new tissue from progenitors at the posterior embryonic end. Axial extension involves different mechanisms that produce internal organs in the trunk but not in the tail. We show that Gdf11 signaling is a major coordinator of the trunk-to-tail transition. Without Gdf11 signaling, the switch from trunk to tail is significantly delayed, and its premature activation brings the hindlimbs and cloaca next to the forelimbs, leaving extremely short trunks. Gdf11 activity includes activation of Isl1 to promote formation of the hindlimbs and cloaca-associated mesoderm as the most posterior derivatives of lateral mesoderm progenitors. Gdf11 also coordinates reallocation of bipotent neuromesodermal progenitors from the anterior primitive streak to the tail bud, in part by reducing the retinoic acid available to the progenitors. Our findings provide a perspective to understand the evolution of the vertebrate body plan.Fundação para a Ciência e a Tecnologia grants: (PTDC/BIA-BCM/110638/2009, PTDC/SAU-BID/110640/2009); FCT PhD fellowships: (SFRH/BD/33562/2008, SFRH/BD/51876/2012, SFRH/BD/51879/2012)

A tale from TGF-β superfamily for thymus ontogeny and function

Multiple signaling pathways control every aspect of cell behavior, organ formation and tissue homeostasis throughout the lifespan of any individual. This review takes an ontogenetic view focused on the large superfamily of TGF-β/BMP ligands to address thymus morphogenesis and function in T cell differentiation. Recent findings on a role of GDF11 for reversing aging-related phenotypes are also discussed

Gene function in schistosomes: recent advances towards a cure

Schistosomes are human parasites distributed worldwide in tropical and sub-tropical latitudes, especially in developing countries and impoverished regions. These neglected tropical disease (NTD) pathogens causes debilitating illnesses, which include hepatosplenomegaly, hepatic fibrosis, haemorrhagic necrotic ulcerations in the intestinal mucosa, urogenital tract diseases, in addition to cardiopulmonary, renal and neurologic lesions due to egg accumulation in the liver, intestines, uro-genital tissues and other sites. Urogenital schistosomiasis is a risk factor for bladder cancer and increases the risk of transmission of HIV infection. Despite extensive effort to control this NTD over the years, deployment on a considerable scale of commercially available drugs in endemic populations has induced the emergence of resistant isolates and raised the need to identify new targets for alternative therapies. Because of the availability of genomes of the three major species of human schistosomiasis, and through advances in functional genomics and live imaging, studies on schistosomes have now come into focus as models to investigate adaptations to parasitism and developmental biology of trematodes and cestodes, and indeed flatworms and Lophotrochozoans, at large. This Research Topic aims at gathering state-of-art essays on schistosome genetics, genetics, pathobiology and immunobiology. It also aims to highlight advances in understanding of the host-parasite relationship, in paradigms that address this NTD, and to discuss new perspectives and advances in chemotherapy and immunoprophylaxis

Tail Bud Progenitor Activity Relies on a Network Comprising Gdf11, Lin28, and Hox13 Genes

During the trunk-to-tail transition, axial progenitors relocate from the epiblast to the tail bud. Here, we show that this process entails a major regulatory switch, bringing tail bud progenitors under Gdf11 signaling control. Gdf11 mutant embryos have an increased number of such progenitors that favor neural differentiation routes, resulting in a dramatic expansion of the neural tube. Moreover, inhibition of Gdf11 signaling recovers the proliferation ability of these progenitors when cultured in vitro. Tail bud progenitor growth is independent of Oct4, relying instead on Lin28 activity. Gdf11 signaling eventually activates Hox genes of paralog group 13, which halt expansion of these progenitors, at least in part, by down-regulating Lin28 genes. Our results uncover a genetic network involving Gdf11, Lin28, and Hox13 genes controlling axial progenitor activity in the tail bud

Neuroendocrine Control of Macrophage Development and Function

Submitted by Sandra Infurna ([email protected]) on 2019-02-10T19:28:55Z No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-02-10T19:40:25Z (GMT) No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5)Made available in DSpace on 2019-02-10T19:40:25Z (GMT). No. of bitstreams: 1 arnondias_juberg_etal_IOC_2018.pdf: 2042436 bytes, checksum: e62a73d671b9925b43cab1a45f36a80a (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.Macrophages carry out numerous physiological activities that are essential for both systemic and local homeostasis, as well as innate and adaptive immune responses. Their biology is intricately regulated by hormones, neuropeptides, and neurotransmitters, establishing distinct neuroendocrine axes. The control is pleiotropic, including maturation of bone marrow-derived myeloid precursors, cell differentiation into functional subpopulations, cytotoxic activity, phagocytosis, production of inflammatory mediators, antigen presentation, and activation of effector lymphocytes. Additionally, neuroendocrine components modulate macrophage ability to influence tumor growth and to prevent the spreading of infective agents. Interestingly, macrophage-derived factors enhance glucocorticoid production through the stimulation of the hypothalamic–pituitary–adrenal axis. These bidirectional effects highlight a tightly controlled balance between neuroendocrine stimuli and macrophage function in the development of innate and adaptive immune responses. Herein, we discuss how components of neuroendocrine axes impact on macrophage development and function and may ultimately influence inflammation, tissue repair, infection, or cancer progression. The knowledge of the crosstalk between macrophages and endocrine or brain-derived components may contribute to improve and create new approaches with clinical relevance in homeostatic or pathological conditions

Image_1_Neuroendocrine Control of Macrophage Development and Function.TIF

<p>Macrophages carry out numerous physiological activities that are essential for both systemic and local homeostasis, as well as innate and adaptive immune responses. Their biology is intricately regulated by hormones, neuropeptides, and neurotransmitters, establishing distinct neuroendocrine axes. The control is pleiotropic, including maturation of bone marrow-derived myeloid precursors, cell differentiation into functional subpopulations, cytotoxic activity, phagocytosis, production of inflammatory mediators, antigen presentation, and activation of effector lymphocytes. Additionally, neuroendocrine components modulate macrophage ability to influence tumor growth and to prevent the spreading of infective agents. Interestingly, macrophage-derived factors enhance glucocorticoid production through the stimulation of the hypothalamic–pituitary–adrenal axis. These bidirectional effects highlight a tightly controlled balance between neuroendocrine stimuli and macrophage function in the development of innate and adaptive immune responses. Herein, we discuss how components of neuroendocrine axes impact on macrophage development and function and may ultimately influence inflammation, tissue repair, infection, or cancer progression. The knowledge of the crosstalk between macrophages and endocrine or brain-derived components may contribute to improve and create new approaches with clinical relevance in homeostatic or pathological conditions.</p

Morphological effects on helminth parasites caused by herbicide under experimental conditions

<div><p>Abstract Helminth parasites have been studied as potential accumulators for different pollutants. Echinostoma paraensei is a foodborne trematode whose vertebrate host, the rodent Nectomys squamipes, is naturally exposed to environmental pesticides. However, little information exists regarding the pesticide’s effects on helminths. This study investigated the morphological effects on the trematode, E. paraensei, after experimental Roundup® herbicide exposure, in concentrations below those recommended for agricultural use. After two hours of exposure, scanning electron microscopy (SEM) showed changes to the tegument, such as furrowing, shrinkage, peeling, spines loss on the peristomic collar, and histopathological evidence of altered cells in the cecum and acinus vitelline glands with vacuoles and structural changes to the muscular layers. Glycidic content was decreased, primarily in the connective tissue. As E. paraensei is an intestinal parasite of the semi-aquatic wild rodent, N. squamipes, it is predisposed to pesticide exposure resulting from agricultural practices. Therefore, we emphasize the need to evaluate its impact on helminth parasites, due to their pivotal role in regulating host populations.</p></div