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      Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning

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          Abstract

          The thyroid and lungs originate as neighboring bud shaped outgrowths from the midline of the embryonic foregut. When and how organ specific programs regulate development into structures of distinct shapes, positions and functions is incompletely understood. To characterize, at least in part, the genetic basis of these events, we have employed laser capture microdissection and microarray analysis to define gene expression in the mouse thyroid and lung primordia at E10.5. By comparing the transcriptome of each bud to that of the whole embryo as well as to each other, we broadly describe the genes that are preferentially expressed in each developing organ as well as those with an enriched expression common to both. The results thus obtained provide a valuable resource for further analysis of genes previously unrecognized to participate in thyroid and lung morphogenesis and to discover organ specific as well as common developmental mechanisms. As an initial step in this direction we describe a regulatory pathway involving the anti-apoptotic gene Bcl2 that controls cell survival in early thyroid development.

          Highlights

          ► The transcriptomes of the early thyroid and lung primordia are characterized. ► Organ-specific and common motifs of gene expression are identified and validated. ► The data provide a resource for finding genes regulating foregut patterning. ► A mechanism involving Bcl2 controls cell survival in the thyroid primordium.

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          Most cited references70

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          DAVID: Database for Annotation, Visualization, and Integrated Discovery.

          Functional annotation of differentially expressed genes is a necessary and critical step in the analysis of microarray data. The distributed nature of biological knowledge frequently requires researchers to navigate through numerous web-accessible databases gathering information one gene at a time. A more judicious approach is to provide query-based access to an integrated database that disseminates biologically rich information across large datasets and displays graphic summaries of functional information. Database for Annotation, Visualization, and Integrated Discovery (DAVID; http://www.david.niaid.nih.gov) addresses this need via four web-based analysis modules: 1) Annotation Tool - rapidly appends descriptive data from several public databases to lists of genes; 2) GoCharts - assigns genes to Gene Ontology functional categories based on user selected classifications and term specificity level; 3) KeggCharts - assigns genes to KEGG metabolic processes and enables users to view genes in the context of biochemical pathway maps; and 4) DomainCharts - groups genes according to PFAM conserved protein domains. Analysis results and graphical displays remain dynamically linked to primary data and external data repositories, thereby furnishing in-depth as well as broad-based data coverage. The functionality provided by DAVID accelerates the analysis of genome-scale datasets by facilitating the transition from data collection to biological meaning.
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            Preparing for the first breath: genetic and cellular mechanisms in lung development.

            The mammalian respiratory system--the trachea and the lungs--arises from the anterior foregut through a sequence of morphogenetic events involving reciprocal endodermal-mesodermal interactions. The lung itself consists of two highly branched, tree-like systems--the airways and the vasculature--that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as branching morphogenesis, vascular development, and the differentiation of multipotent progenitor populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding respiratory disorders, congenital defects in human neonates, and how the disruption of morphogenetic programs early in lung development can lead to deficiencies that persist throughout life. (c) 2010 Elsevier Inc. All rights reserved.
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              Fgf10 is essential for limb and lung formation.

              The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10-/- mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.
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                Author and article information

                Journal
                Dev Biol
                Dev. Biol
                Developmental Biology
                Elsevier
                0012-1606
                1095-564X
                15 November 2011
                15 November 2011
                : 359
                : 2
                : 163-175
                Affiliations
                [a ]IRGS, Biogem, Ariano Irpino (AV), Italy
                [b ]Stazione Zoologica Anton Dohrn, Naples, Italy
                [c ]Dipartimento di Biologia e Patologia, Università di Napoli Federico II, Naples, Italy
                [d ]Dipartimento di Scienze Biologiche ed Ambientali, Università del Sannio, Benevento, Italy
                Author notes
                [* ]Corresponding author at: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Via Pansini 5, 80131 Napoli, Italy. Fax: +390817463749. roberto.dilauro@ 123456szn.it
                [1]

                Co-first authors.

                [2]

                Present Address: Department of Pathology, Institute of Biomedicine, Gothenburg, Sweden.

                [3]

                Present Address: EMBL, Monterotondo (Rome), Italy.

                [4]

                Present Address: Institudo de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.

                Article
                YDBIO5432
                10.1016/j.ydbio.2011.08.015
                3206993
                21924257
                dffffbeb-2f03-49dc-8385-4a036bd42332
                © 2011 Elsevier Inc.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 1 March 2011
                : 24 August 2011
                Categories
                Resource

                Developmental biology
                lcm,organogenesis,lung bud,microarrays,thyroid bud,foregut patterning
                Developmental biology
                lcm, organogenesis, lung bud, microarrays, thyroid bud, foregut patterning

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