Modulation of BMP Activity in Dorsal-Ventral Pattern Formation by the Chordin and Ogon Antagonists

Developmental Biology

Mary C. Mullins¹  Daniel S. Wagner¹ 

[1] Department of Cell and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, Pennsylvania, 19104

关键词: Zebrafish;    Danio rerio;    dorsal–ventral;    BMP;    BMP antagonist;    Chordin;    pattern formation;   

DOI  :  10.1006/dbio.2002.0614

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

WeanalyzedtheinteractionsbetweenmutationsinantagonisticBMPpathwaysignalingcomponentstoexaminetherolesthattheantagonistsplayinregulatingBMPsignalingactivity.Thedorsalizedmutantsswirl/bmp2b,snailhouse/bmp7,lost-a-fin/alk8,andminifin/tolloidwereeachanalyzedindoublemutantcombinationswiththeventralizedmutantschordino/chordinandogon,whosemolecularnatureisnotknown.SimilartotheBMPantagonistchordino,wefoundthattheBMPligandmutantsswirl/bmp2bandsnailhouse/bmp7arealsoepistatictotheputativeBMPpathwayantagonist,ogon,excludingaclassofintracellularantagonistsascandidatesforogon.Inogon;minifindoublemutants,weobservedamutualsuppressionoftheogonandminifinmutantphenotypes,frequentlytoawildtypephenotype.Thus,theTolloid/MinifinmetalloproteasethatnormallycleavesandinhibitsChordinactivityisdispensable,whenOgonantagonismisreduced.TheseresultssuggestthatOgonencodesaTolloidandChordin-independentantagonisticfunction.ByanalyzinggeneswhoseexpressionisverysensitivetoBMPsignalinglevels,wefoundthattheabsenceofOgonorChordinantagonismdidnotincreasetheBMPactivityremaininginswirl/bmp2borhypomorphicsnailhouse/bmp7mutants.Theseresults,togetherwithotherstudies,suggestthatadditionalmoleculesormechanismsareessentialingeneratingthepresumptivegastrulaBMPactivitygradientthatpatternsthedorsal–ventralaxis.Lastlyweobservedastrikingincreasedpenetranceoftheswirl/bmp2bdominantdorsalizedphenotype,whenChordinfunctionisalsoabsent.LossoftheBMPantagonistChordinisexpectedtoincreaseBMPsignalinglevelsinaswirlheterozygote,butinsteadweobservedanapparentdecreaseinBMPsignalinglevelsandalossofventraltailtissue.Ashasbeenproposedfortheflyorthologueofchordin,shortgastrulation,ourparadoxicalresultscanbeexplainedbyamodelwherebyChordinbothantagonizesandpromotesBMPactivity.

【 授权许可】

Unknown