Browsing by MeSH term "Organogenesis"
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Publication 4D reconstruction of murine developmental trajectories using spherical harmonics.(Cell Press, 2022-09-12) Dalmasso, Giovanni; Musy, Marco; Niksic, Martina; Robert-Moreno, Alexandre; Badia-Careaga, Claudio; Sanz-Ezquerro, Juan Jose; Sharpe, James; European Molecular Biology Laboratory; Unión Europea. Comisión Europea. European Research Council (ERC); Fundación La Marató TV3Normal organogenesis cannot be recapitulated in vitro for mammalian organs, unlike in species including Drosophila and zebrafish. Available 3D data in the form of ex vivo images only provide discrete snapshots of the development of an organ morphology. Here, we propose a computer-based approach to recreate its continuous evolution in time and space from a set of 3D volumetric images. Our method is based on the remapping of shape data into the space of the coefficients of a spherical harmonics expansion where a smooth interpolation over time is simpler. We tested our approach on mouse limb buds and embryonic hearts. A key advantage of this method is that the resulting 4D trajectory can take advantage of all the available data while also being able to interpolate well through time intervals for which there are little or no data. This allows for a quantitative, data-driven 4D description of mouse limb morphogenesis.Publication Loss of GATA4 causes ectopic pancreas in the stomach.(Wiley, 2020-04) Rodríguez-Seguel, Elisa; Villamayor, Laura; Arroyo, Noelia; De Andrés, Mónica P; Real Arribas, Francisco; Martín, Franz; Cano, David A; Rojas, Anabel; Ministerio de Ciencia y Universidades (España)Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox ; Pdx1-Cre mice (Gata4KO mice). We found that Gata4KO glandular epithelium displays an atypical morphology similar to the cornified squamous epithelium and exhibits upregulation of forestomach markers. The developing gastric units fail to form properly, and the glandular epithelial cells do not express markers of gastric gland in the absence of GATA4. Of interest, the developing glands of the Gata4KO stomach express pancreatic cell markers. Furthermore, a mass of pancreatic tissue located in the subserosa of the Gata4KO stomach is observed at adult stages. Heterotopic pancreas found in Gata4-deficient mice contains all three pancreatic cell lineages: ductal, acinar, and endocrine. Moreover, Gata4 expression is downregulated in ectopic pancreatic tissue of some human biopsy samples. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Publication Lymphoangiocrine signals promote cardiac growth and repair.(Nature Publishing Group, 2020-12) Liu, Xiaolei; De la Cruz, Ester; Gu, Xiaowu; Balint, Laszlo; Oxendine-Burns, Michael; Terrones, Tamara; Ma, Wanshu; Kuo, Hui-Hsuan; Lantz, Connor; Bansal, Trisha; Thorp, Edward; Burridge, Paul; Jakus, Zoltán; Herz, Joachim; Cleaver, Ondine; Torres, Miguel; Oliver, Guillermo; Ministerio de Educación (España); European Molecular Biology Organization; Ministerio de Ciencia e Innovación (España); National Institutes of Health (Estados Unidos)Recent studies have suggested that lymphatics help to restore heart function after cardiac injury1-6. Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction. Embryos that lack LECs develop smaller hearts as a consequence of reduced cardiomyocyte proliferation and increased cardiomyocyte apoptosis. Culturing primary mouse cardiomyocytes in LEC-conditioned medium increases cardiomyocyte proliferation and survival, which indicates that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function.Publication Myc is dispensable for cardiomyocyte development but rescues Mycn-deficient hearts through functional replacement and cell competition.(The Company of Biologists, 2019-02-01) Munoz Martin, Noelia; Sierra, Rocio; Schimmang, Thomas; Villa del Campo, Cristina; Torres, Miguel; Fondation Leducq; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Fundación La Caixa; Fundación ProCNICMyc is considered an essential transcription factor for heart development, but cardiac defects have only been studied in global Myc loss-of-function models. Here, we eliminated Myc by recombining a Myc floxed allele with the Nkx2.5Cre driver. We observed no anatomical, cellular or functional alterations in either fetuses or adult cardiac Myc-deficient mice. We re-examined Myc expression during development and found no expression in developing cardiomyocytes. In contrast, we confirmed that Mycn is essential for cardiomyocyte proliferation and cardiogenesis. Mosaic Myc overexpression in a Mycn-deficient background shows that Myc can replace Mycn function, recovering heart development. We further show that this recovery involves the elimination of Mycn-deficient cells by cell competition. Our results indicate that Myc is dispensable in cardiomyocytes both during cardiogenesis and for adult heart homeostasis, and that Mycn is exclusively responsible for cardiomyocyte proliferation during heart development. Nonetheless, our results show that Myc can functionally replace Mycn We also show that cardiomyocytes compete according to their combined Myc and Mycn levels and that cell competition eliminates flawed cardiomyocytes, suggesting its relevance as a quality control mechanism in cardiac development.Publication Notch and interacting signalling pathways in cardiac development, disease, and regeneration.(Springer, 2018-10) MacGrogan, Donal; Munch, Juliane; de la Pompa, Jose Luis; Ministerio de Ciencia, Innovación y Universidades (España); Fundación BBVA; Fundación La Marató TV3; Fundación ProCNIC; Centro de Investigación Biomedica en Red - CIBERCardiogenesis is a complex developmental process involving multiple overlapping stages of cell fate specification, proliferation, differentiation, and morphogenesis. Precise spatiotemporal coordination between the different cardiogenic processes is ensured by intercellular signalling crosstalk and tissue-tissue interactions. Notch is an intercellular signalling pathway crucial for cell fate decisions during multicellular organismal development and is aptly positioned to coordinate the complex signalling crosstalk required for progressive cell lineage restriction during cardiogenesis. In this Review, we describe the role of Notch signalling and the crosstalk with other signalling pathways during the differentiation and patterning of the different cardiac tissues and in cardiac valve and ventricular chamber development. We examine how perturbation of Notch signalling activity is linked to congenital heart diseases affecting the neonate and adult, and discuss studies that shed light on the role of Notch signalling in heart regeneration and repair after injury.Publication Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.(Cell Press, 2022-05-12) Chen, Ao; Liao, Sha; Cheng, Mengnan; Ma, Kailong; Wu, Liang; Lai, Yiwei; Qiu, Xiaojie; Yang, Jin; Xu, Jiangshan; Hao, Shijie; Wang, Xin; Lu, Huifang; Chen, Xi; Liu, Xing; Huang, Xin; Li, Zhao; Hong, Yan; Jiang, Yujia; Peng, Jian; Liu, Shuai; Shen, Mengzhe; Liu, Chuanyu; Li, Quanshui; Yuan, Yue; Wei, Xiaoyu; Zheng, Huiwen; Feng, Weimin; Wang, Zhifeng; Liu, Yang; Wang, Zhaohui; Yang, Yunzhi; Xiang, Haitao; Han, Lei; Qin, Baoming; Guo, Pengcheng; Lai, Guangyao; Muñoz-Cánoves, Pura; Maxwell, Patrick H; Thiery, Jean Paul; Wu, Qing-Feng; Zhao, Fuxiang; Chen, Bichao; Li, Mei; Dai, Xi; Wang, Shuai; Kuang, Haoyan; Hui, Junhou; Wang, Liqun; Fei, Ji-Feng; Wang, Ou; Wei, Xiaofeng; Lu, Haorong; Wang, Bo; Liu, Shiping; Gu, Ying; Ni, Ming; Zhang, Wenwei; Mu, Feng; Yin, Ye; Yang, Huanming; Lisby, Michael; Cornall, Richard J; Mulder, Jan; Uhlén, Mathias; Esteban, Miguel A; Li, Yuxiang; Liu, Longqi; Xu, Xun; Wang, JianSpatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.Publication Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.(The Company of Biologists, 2021-01) Cahill, Thomas J; Sun, Xin; Ravaud, Christophe; Villa del Campo, Cristina; Klaourakis, Konstantinos; Lupu, Irina-Elena; Lord, Allegra M; Browne, Cathy; Jacobsen, Sten Eirik W; Greaves, David R; Jackson, David G; Cowley, Sally A; James, William; Choudhury, Robin P; Vieira, Joaquim Miguel; Riley, Paul R; British Heart Foundation; BHF Oxbridge Centre of Regenerative Medicine; Wellcome Trust; BHF Intermediate Basic Science Research; British Council. BIRAX (British Israel Research and Academic Exchange Partnership); Fondation LeducqMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.