48 research outputs found

    Identification of Pax6-Dependent Gene Regulatory Networks in the Mouse Lens

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    Lineage-specific DNA-binding transcription factors regulate development by activating and repressing particular set of genes required for the acquisition of a specific cell type. Pax6 is a paired domain and homeodomain-containing transcription factor essential for development of central nervous, olfactory and visual systems, as well as endocrine pancreas. Haploinsufficiency of Pax6 results in perturbed lens development and homeostasis. Loss-of-function of Pax6 is incompatible with lens lineage formation and results in abnormal telencephalic development. Using DNA microarrays, we have identified 559 genes expressed differentially between 1-day old mouse Pax6 heterozygous and wild type lenses. Of these, 178 (31.8%) were similarly increased and decreased in Pax6 homozygous embryonic telencephalon [Holm PC, Mader MT, Haubst N, Wizenmann A, Sigvardsson M, Götz M (2007) Loss- and gain-of-function analyses reveals targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci 34: 99–119]. In contrast, 381 (68.2%) genes were differently regulated between the lens and embryonic telencephalon. Differential expression of nine genes implicated in lens development and homeostasis: Cspg2, Igfbp5, Mab21l2, Nrf2f, Olfm3, Spag5, Spock1, Spon1 and Tgfb2, was confirmed by quantitative RT-PCR, with five of these genes: Cspg2, Mab21l2, Olfm3, Spag5 and Tgfb2, identified as candidate direct Pax6 target genes by quantitative chromatin immunoprecipitation (qChIP). In Mab21l2 and Tgfb2 promoter regions, twelve putative individual Pax6-binding sites were tested by electrophoretic mobility shift assays (EMSAs) with recombinant Pax6 proteins. This led to the identification of two and three sites in the respective Mab21l2 and Tgfb2 promoter regions identified by qChIPs. Collectively, the present studies represent an integrative genome-wide approach to identify downstream networks controlled by Pax6 that control mouse lens and forebrain development

    Current management of the gastrointestinal complications of systemic sclerosis.

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    Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation

    The temporal dynamics of temporary pond macroinvertebrate communities over a 10-year period

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    Ponds support a rich biodiversity. This arises in part because of the number and heterogeneity of ponds spatially throughout the landscape. Studies of ponds suggest that distinct communities develop within individual ponds but most examples are based on shortterm 1- or 2-year surveys which cannot identify the effects of historic events upon contemporary communities. This study reports the development and turnover of the early summer macroinvertebrate communities in thirty small temporary ponds fromtheir creation in 1994 over 10 years to 2004. Distinct pioneer communities established in the first year of the ponds’ creation, the first 3 years dominated by a fauna associated with long summer dry phases. Then a sustained period of inundation lasting 27 months from summer 1997–1999 resulted in establishment of many taxa associated with permanent ponds and loss of some temporary pond species. The re-establishment of summer dry phases in 1999 was associated with the loss of some but not all of the permanent water taxa and re-colonisation by some temporary water species creating new communities combining these different elements. The communities were not a linear successional sequence; the communities that re-assembled following resumption of dry phases reflected the contingent history of each pond and the effects of historic events. The longer term nature of the study showed that the characteristic heterogeneity of pond invertebrate communities occurs through time as well as spatially and that the richness and variety of contemporary communities, which is often hard to explain fromsnap-shot studies, is partly the result of historic events
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