The Experts below are selected from a list of 2568 Experts worldwide ranked by ideXlab platform
Maxime Bouchard - One of the best experts on this subject based on the ideXlab platform.
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coordinated cell behaviours in early urogenital system morphogenesis
Seminars in Cell & Developmental Biology, 2014Co-Authors: Katherine Stewart, Maxime BouchardAbstract:Abstract The elaboration of functional kidneys during embryonic development proceeds in a stepwise manner, starting with the formation of the embryonic pro- and Mesonephros, followed by the induction and growth of the final metanephric kidney. These early stages of urinary tract development are critical for the embryo as a failure in pro/Mesonephros morphogenesis leads to major developmental defects, often incompatible with life. The formation of the pro/Mesonephros and its central component the nephric duct, is also interesting as it offers a relatively simple system to study cell biological behaviours underlying tissue morphogenesis. This system is especially well adapted to study the questions of cell lineage specification, epithelial integrity and plasticity, tissue interactions, collective cell migration/guidance and programmed cell death. In this review, we establish the link between these cell behaviours, their molecular regulators and early genitourinary tract development.
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a core transcriptional network composed of pax2 8 gata3 and lim1 regulates key players of pro Mesonephros morphogenesis
Developmental Biology, 2013Co-Authors: Sami Kamel Boualia, Yaned Gaitan, Mathieu Tremblay, Richa Sharma, Julie Cardin, Artur Kania, Maxime BouchardAbstract:Abstract Translating the developmental program encoded in the genome into cellular and morphogenetic functions requires the deployment of elaborate gene regulatory networks (GRNs). GRNs are especially crucial at the onset of organ development where a few regulatory signals establish the different programs required for tissue organization. In the renal system primordium (the pro/Mesonephros), important regulators have been identified but their hierarchical and regulatory organization is still elusive. Here, we have performed a detailed analysis of the GRN underlying mouse pro/Mesonephros development. We find that a core regulatory subcircuit composed of Pax2/8, Gata3 and Lim1 turns on a deeper layer of transcriptional regulators while activating effector genes responsible for cell signaling and tissue organization. Among the genes directly affected by the core components are the key developmental molecules Nephronectin (Npnt) and Plac8. Hence, the pro/Mesonephros GRN links together several essential genes regulating tissue morphogenesis. This renal GRN sheds new light on the disease group Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in that gene mutations are expected to generate different phenotypic outcomes as a consequence of regulatory network deficiencies rather than threshold effects from single genes.
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live imaging of the developing mouse Mesonephros
Methods of Molecular Biology, 2012Co-Authors: David Grote, Michael Marcotte, Maxime BouchardAbstract:Embryonic development is a highly dynamic process involving complex tissue interactions and movements. Recent progress in cell labeling, image acquisition, and image processing technologies has brought the study of embryo morphogenesis to another level. It is now possible to visualize in real time the dynamic morphogenetic changes occurring in vivo and to reconstitute and quantify them in 4D rendering. However, extended live embryo imaging remains challenging in terms of embryo survival and minimization of phototoxicity. Here, we describe a procedure to image the developing Mesonephros for up to 16 h in intact mouse embryos. This method can easily be adapted to the imaging of other structures at similar developmental stages.
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pax2 8 regulated gata3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney
Development, 2006Co-Authors: David Grote, Abdallah Souabni, Meinrad Busslinger, Maxime BouchardAbstract:The mammalian pro- and Mesonephros are transient embryonic kidneys essential for urogenital system development. The nephric (Wolffian) duct, which is a central constituent of both structures, elongates caudally along a stereotypical path to reach the hindlimb level where it induces metanephros (adult kidney) formation, while the remaining duct gives rise to the male genital tract (epidydimis, vas deferens). The transcription factors Pax2 and Pax8 are essential for the initiation of pro- and Mesonephros development. In a cDNA microarray screen for genes specifically expressed in the pro/Mesonephros and regulated by Pax proteins, we identified Gata3, a transcription factor gene associated with hypoparathyroidism, deafness and renal anomaly (HDR) syndrome. Gata3 is already expressed in the pronephric anlage, together with Pax2 and Pax8, suggesting that it may be a direct Pax2/8 target gene. Inactivation of Gata3 by insertion of an Ires-GFP reporter gene resulted in a massive increase in nephric duct cellularity, which was accompanied by enhanced cell proliferation and aberrant elongation of the nephric duct. Interestingly, however, the nephrogenic cord extended, with delayed kinetics, along the entire caudal path up to the level of the hindlimb bud, indicating that extension of the nephric duct and cord is controlled by different guidance cues. At the molecular level, the nephric duct of Gata3-/- embryos is characterized by the loss of Ret expression and signaling, which may contribute to the guidance defect of the nephric duct. Together, these results define Gata3 as a key regulator of nephric duct morphogenesis and guidance in the pro/mesonephric kidney.
Anne C Fergusonsmith - One of the best experts on this subject based on the ideXlab platform.
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dlk1 is a negative regulator of emerging hematopoietic stem and progenitor cells
Haematologica, 2013Co-Authors: Marella F.t.r. De Bruijn, Esther Haak, Gillian M Kimber, Kevin Van Leusden, Kirsty N Harvey, John Orourke, Jorge Laborda, Steven R Bauer, Bahar Mirshekarsyahkal, Anne C FergusonsmithAbstract:The first mouse adult-repopulating hematopoietic stem cells emerge in the aorta-gonad-Mesonephros region at embryonic day (E) 10.5. Their numbers in this region increase thereafter and begin to decline at E12.5, thus pointing to the possible existence of both positive and negative regulators of emerging hematopoietic stem cells. Our recent expression analysis of the aorta-gonad-Mesonephros region showed that the Delta-like homologue 1 (Dlk1) gene is up-regulated in the region of the aorta-gonad-Mesonephros where hematopoietic stem cells are preferentially located. To analyze its function, we studied Dlk1 expression in wild-type and hematopoietic stem cell-deficient embryos and determined hematopoietic stem and progenitor cell activity in Dlk1 knockout and overexpressing mice. Its role in hematopoietic support was studied in co-culture experiments using stromal cell lines that express varying levels of Dlk1. We show here that Dlk1 is expressed in the smooth muscle layer of the dorsal aorta and the ventral sub-aortic mesenchyme, where its expression is dependent on the hematopoietic transcription factor Runx1. We further demonstrate that Dlk1 has a negative impact on hematopoietic stem and progenitor cell activity in the aorta-gonad-Mesonephros region in vivo, which is recapitulated in co-cultures of hematopoietic stem cells on stromal cells that express varying levels of Dlk1. This negative effect of Dlk1 on hematopoietic stem and progenitor cell activity requires the membrane-bound form of the protein and cannot be recapitulated by soluble Dlk1. Together, these data suggest that Dlk1 expression by cells of the aorta-gonad-Mesonephros hematopoietic microenvironment limits hematopoietic stem cell expansion and is, to our knowledge, the first description of such a negative regulator in this tissue.
Amelio Dolfi - One of the best experts on this subject based on the ideXlab platform.
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immunohistochemical localization of the epidermal growth factor transforming growth factor α and their receptor in the human Mesonephros and metanephros
Developmental Dynamics, 1996Co-Authors: Nunzia Bernardini, F Bianchi, M Lupetti, Amelio DolfiAbstract:The distribution of epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and EGF/TGF alpha receptor were studied by means of immunohistochemical methods starting from the very early stages of human embryonic kidney development. Mesonephros and metanephros were examined in order to detect immunoreactive staining in serial sectioned embryos and fetal kidneys. Anti-EGF immunoprecipitates were found in the S-shaped mesonephric vesicles of 6-week old embryos as well as in the mesonephric duct albeit with a lower degree of reactivity. Intense reactivity was observed in the metanephros within the blastemic caps of the same gestational period; the reaction was weaker within the ureteric bud branches. Bowman's capsule, proximal tubules, and collecting ducts were also reactive in the fetal kidney to varying degrees. The distribution of TGF alpha reactivity in the Mesonephros was similar to that observed for EGF but with a lower intensity. In contrast, there was no reactivity in the metanephros, at least during the embyronic periods examined. By the 11th week of gestation, an intense reactivity for TGF alpha polipeptide was shown in the fetal kidney at the level of the proximal tubules and Bowman's capsule; distal tubules as well as all urinary structures from the collecting ducts to the pelvis were less reactive. Finally, EGF/TGF alpha receptor reactivity was identified by the 6th week of development, being more intense in the Mesonephros at the level of the mesonephric duct cells. In the metanephros, the ureteric bud-derived branches were reactive, whereas most of the blastemic tissue did not stain. By the 11th week, only the collecting ducts and the remaining urinary structures contained reaction products: Reactivity was distributed to the tissues originating from the ureteric bud branching. Taking into account recent advances in knowledge about the biology of growth factors, the hypothesis is proposed that the secretory components (vesicles, glomerulus, and tubules) of renal anlagen might release the growth factors while the cells of the urinary tract (i.e., collecting duct, pelvis, etc.) may be their targets.
Michael Solursh - One of the best experts on this subject based on the ideXlab platform.
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effects of the Mesonephros and insulin like growth factor i on chondrogenesis of limb explants
Developmental Biology, 1993Co-Authors: Jane S Geduspan, Michael SolurshAbstract:The Mesonephros has been shown to have a growth-promoting influence in vivo on limb outgrowth. This influence has been studied in detail using an organ culture system. The results show that in the presence of the Mesonephros limb explants formed larger cartilages than cultures without Mesonephros. Furthermore, with Mesonephros, morphology of the cartilages is comparable to that of skeletal elements in vivo while cartilages formed in cultures lacking Mesonephros were amorphous. The mesonephric influence also promoted the formation of a well-organized extracellular matrix in the cartilage while cartilage in cultures without Mesonephros formed an abnormal appearing matrix. Cartilage matrices in cultures with or without Mesonephros were immunoreactive to type IX and type II collagens, cartilage proteoglycan PGH, and link protein although cultures lacking Mesonephros had a very restricted distribution of type IX collagen immunoreactivity. Despite the different distribution of type IX collagen, long-form-type IX collagen transcripts appeared similar in both types of culture based on in situ hybridization. The mesonephric effect on limb explants could be partially duplicated by the addition of insulin-like growth factor I (IGF-I) to cultures without Mesonephros. Furthermore, the mesonephric influence on cartilage growth and morphological differentiation could be blocked by the addition of a blocking antibody to IGF-I to cultures with Mesonephros. The results support the hypothesis that IGF-I is one of the growth factors produced by the Mesonephros which may play a role in early limb development and chondrogenesis.
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a growth promoting influence from the Mesonephros during limb outgrowth
Developmental Biology, 1992Co-Authors: Jane S Geduspan, Michael SolurshAbstract:Abstract It has been suggested that the Mesonephros has a role in normal limb development. This hypothesis was directly tested by removing the Mesonephros adjacent to the presumptive limb region of stage 12–18 chick embryos using microsurgery or laser ablation. The experimental manipulation resulted in reduced limb outgrowth on the operated side. The poor limb outgrowth was correlated with either the lack of or the presence of a rudimentary Mesonephros on the operated side. Furthermore, the presence of nephric tissue in limb bud organ culture enhanced growth and morphological differentiation of cartilage formed in culture. In vivo, the influence of the Mesonephros resulted in significantly higher cell proliferation in the adjoining medial half of the limb mesoderm compared with the lateral half. The removal of the Mesonephros adjoining the prospective limb region reduced the number of dividing cells in the medial mesoderm. The higher proliferation in the medial limb mesoderm is significant to limb outgrowth since grafting experiments showed that most of the cells that form the limb are derived from the medial mesoderm. The results suggest that the influence from the Mesonephros may provide some signal for limb outgrowth.
Elaine Dzierzak - One of the best experts on this subject based on the ideXlab platform.
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Mesenchymal lineage potentials of aorta-gonad-Mesonephros stromal clones.
Haematologica, 2006Co-Authors: Charles Durand, Catherine Robin, Elaine DzierzakAbstract:BACKGROUND AND OBJECTIVES: The characterization of stem cell microenvironments throughout ontogeny is of fundamental interest in the field of stem cell biology. Within the adult blood system, hematopoietic stem cells (HSC) are supported in the osteoblastic and endothelial bone marrow microenvironments. During mouse mid-gestation, the first HSC emerge autonomously in the aorta-gonad-Mesonephros (AGM) region. However, little is known about this microenvironment. To study the cellular complexity of the AGM hematopoietic microenvironment and its relationship to HSC, we examined the potential of AGM stromal clones to differentiate into several mesenchymal lineages. DESIGN AND METHODS: Stromal cell clones from the mid-gestation mouse were cultured in appropriate conditions known to support osteogenic, adipogenic, chondrogenic and endothelial differentiation. Potentials of the stromal cells were scored by morphological examination of the cultures, specific staining and gene expression profile. RESULTS: We show that most clones possess uni/bilineage osteogenic, adipogenic and/or endothelial potential. The differentiation potential of the stromal clones appears to relate to their site of origin but not to their ability to support hematopoiesis. Moreover, we show that AGM HSC activity is unaffected by the osteogenic differentiation of UG26.1B6 stromal cells. INTERPRETATION AND CONCLUSIONS: These results confirm the existence of mesenchymal stem/progenitor cells in the AGM region and suggest that the AGM hematopoietic microenvironment is highly complex, containing stromal cells with various mesenchymal lineage potentials.
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Stromal cells from murine embryonic aorta-gonad-Mesonephros region, liver and gut mesentery expand human umbilical cord blood-derived CAFC(week6) in extended long-term cultures.
Leukemia, 2002Co-Authors: Nuray Kusadasi, Elaine Dzierzak, Robert A.j. Oostendorp, Wendy Koevoet, Rob E. PloemacherAbstract:Stromal cells from murine embryonic aorta–gonad–Mesonephros region, liver and gut mesentery expand human umbilical cord blood-derived CAFC week6 in extended long-term cultures