In Vivo Evidence That BMP Signaling Is Necessary for Apoptosis in the Mouse Limb

Developmental Biology

Udayan Guha¹  Tatsuya Kobayashi¹  Richard G. Pestell¹  John A. Kessler¹  William A. Gomes¹ 

[1] Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, 10461

关键词: BMP;    Noggin;    limb development;    apoptosis;    Msx;    Hox;    FGF8;    keratin 14;   

DOI  :  10.1006/dbio.2002.0752

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

TodeterminetheroleofBonemorphogeneticprotein(BMP)signalinginmurinelimbdevelopmentinvivo,thekeratin14promoterwasusedtodriveexpressionoftheBMPantagonistNogginintransgenicmice.PhosphorylationandnucleartranslocationofSmad1/5weredramaticallyreducedinlimbsofthetransgenicanimals,confirmingtheinhibitionofBMPsignaling.Thesemicedevelopedextensivelimbsofttissuesyndactylyandpostaxialpolydactyly.Apoptosisinthedevelopinglimbnecroticzoneswasreducedwithincompleteregressionoftheinterdigitaltissue.ThepostaxialextradigitisalsoconsistentwitharoleforBMPsinregulatingapoptosis.Furthermore,therewaspersistentexpressionofFgf8,suggestingadelayintheregressionoftheAER.However,Msx1andMsx2expressionwasunchangedinthesetransgenicmice,implyingthatinductionofthesegenesisnotessentialformediatingBMP-inducedinterdigitalapoptosisinmice.TheseabnormalitieswererescuedbycoexpressingBMP4underthesamepromoterindoubletransgenicmice,suggestingthatthelimbabnormalitiesareadirecteffectofinhibitingBMPsignaling.

【 授权许可】

Unknown