Wnt5a Participates in Distal Lung Morphogenesis

Developmental Biology

Parviz Minoo¹  Khadija Hormi¹  Changgong Li¹  Zea Borok¹  Jing Xiao¹ 

[1] Department of Pediatrics, Women's & Children's Hospital, Department of Medicine, USC Keck School of Medicine, Los Angeles, California, 90033

关键词: lung morphogenesis;    lung maturation;    proximal/distal;    Wnt5a;    Shh;    Ptc;    Bmp4;    Nkx2.1;    Fgf-10;    Sprouty;   

DOI  :  10.1006/dbio.2002.0729

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Operationalparallelsinoverallmechanismsofthree-dimensionalpatterningofvertebrateorgansarebecomingincreasinglyapparent.Manykeymediators,suchasFGFs,BMPs,andsonichedgehog,participateinorganizationofanumberoforgans,includingthelungs,whichexhibitadefinedproximodistal(P-D)polarity.Recently,Wnt5aamemberofthewinglessfamilyofsignalingmoleculesinvolvedincellproliferation,differentiation,andorganogenesis,wasshowntounderlietheoutgrowthandP-Dmorphogenesisofthevertebratelimb.Inthecurrentstudy,weshowthatWnt5aisexpressedinthemouselungandplaysanimportantroleinlungdistalmorphogenesis.AnalysisofthemutantphenotypeinmicecarryingatargeteddisruptionoftheWnt5alocusshowsdistinctabnormalitiesindistallungmorphogenesisasmanifestedbydistincttruncationofthetracheaandoverexpansionofthedistalrespiratoryairways.InthefaceofdeletedWNT5aactivity,bothepithelialandmesenchymalcellcompartmentsoftheWnt5a(−/−)lungsexhibitincreasedcellproliferation.Theoverallarchitectureofthemutantlungsischaracterizedbyoverexpansionofthedistalairwaysandinhibitionoflungmaturationasreflectedbypersistenceofthickenedintersaccularinterstitium.AbsenceofWNT5aactivityinthemutantlungsleadstoincreasedexpressionofFgf-10,Bmp4,Shh,anditsreceptorPtc,raisingthepossibilitythatWNT5a,FGF-10,BMP4,andSHHsignalingpathwaysarefunctionallyinteractive.

【 授权许可】

Unknown