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MITF – A controls branching morphogenesis and nephron endowment
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نویسنده
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phelep a. ,laouari d. ,bharti k. ,burtin m. ,tammaccaro s. ,garbay s. ,nguyen c. ,vasseur f. ,blanc t. ,berissi s. ,langa-vives f. ,fischer e. ,druilhe a. ,arnheiter h. ,friedlander g. ,pontoglio m. ,terzi f.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 12
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چکیده
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Congenital nephron number varies widely in the human population and individuals with low nephron number are at risk of developing hypertension and chronic kidney disease. the development of the kidney occurs via an orchestrated morphogenetic process where metanephric mesenchyme and ureteric bud reciprocally interact to induce nephron formation. the genetic networks that modulate the extent of this process and set the final nephron number are mostly unknown. here,we identified a specific isoform of mitf (mitf-a),a bhlh-zip transcription factor,as a novel regulator of the final nephron number. we showed that overexpression of mitf-a leads to a substantial increase of nephron number and bigger kidneys,whereas mitfa deficiency results in reduced nephron number. furthermore,we demonstrated that mitf-a triggers ureteric bud branching,a phenotype that is associated with increased ureteric bud cell proliferation. molecular studies associated with an in silico analyses revealed that amongst the putative mitf-a targets,ret was significantly modulated by mitf-a. consistent with the key role of this network in kidney morphogenesis,ret heterozygosis prevented the increase of nephron number in mice overexpressing mitf-a. collectively,these results uncover a novel transcriptional network that controls branching morphogenesis during kidney development and identifies one of the first modifier genes of nephron endowment. © 2017 public library of science. all rights reserved.
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آدرس
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inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, unit on ocular and stem cells translational research national eye institute,national institutes of health,bethesda,md, United States, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1016—cnrs umr 8104,université paris descartes,institut cochin,paris, France, inserm u1016—cnrs umr 8104,université paris descartes,institut cochin,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, centre d’ingénierie génétique murine,institut pasteur,paris, France, inserm u1016—cnrs umr 8104,université paris descartes,institut cochin,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, scientist emeritus,national institute of neurological disorders and stroke,national institutes of health,10 center drive,bethesda,md, United States, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France, inserm u1016—cnrs umr 8104,université paris descartes,institut cochin,paris, France, inserm u1151—cnrs umr 8253,université paris descartes,institut necker enfants malades,département « croissance et signalisation »,hôpital necker enfants malades,paris, France
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Authors
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