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Alx4 relays sequential FGF signaling to induce lacrimal gland morphogenesis
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نویسنده
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garg a. ,bansal m. ,gotoh n. ,feng g.-s. ,zhong j. ,wang f. ,kariminejad a. ,brooks s. ,zhang x.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 10
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چکیده
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The sequential use of signaling pathways is essential for the guidance of pluripotent progenitors into diverse cell fates. here,we show that shp2 exclusively mediates fgf but not pdgf signaling in the neural crest to control lacrimal gland development. in addition to preventing p53-independent apoptosis and promoting the migration of sox10-expressing neural crests,shp2 is also required for expression of the homeodomain transcription factor alx4,which directly controls fgf10 expression in the periocular mesenchyme that is necessary for lacrimal gland induction. we show that alx4 binds an fgf10 intronic element conserved in terrestrial but not aquatic animals,underlying the evolutionary emergence of the lacrimal gland system in response to an airy environment. inactivation of alx4/alx4 causes lacrimal gland aplasia in both human and mouse. these results reveal a key role of alx4 in mediating fgf-shp2-fgf signaling in the neural crest for lacrimal gland development. © 2017 garg et al.
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آدرس
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departments of ophthalmology,pathology and cell biology,columbia university,new york,ny,united states,department of biochemistry and molecular biology,indiana university school of medicine,indianapolis,in, United States, psychogenics inc.,tarrytown,ny, United States, division of cancer cell biology,cancer research institute,kanazawa university kakuma-machi,kanazawa city, Japan, department of pathology,school of medicine and section of molecular biology,division of biological sciences,university of california san diego,la jolla,ca, United States, burke medical research institute,feil family brain and mind research institute,weill cornell medicine,white plains,ny, United States, center for cancer biology and nutrition,institute of biosciences and technology,texas a&m,houston,tx, United States, kariminejad-najmabadi pathology & genetics center,tehran, ایران, departments of ophthalmology,pathology and cell biology,columbia university,new york,ny, United States, departments of ophthalmology,pathology and cell biology,columbia university,new york,ny, United States
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Authors
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