Mouse GLI3 Regulates Fgf8 Expression and Apoptosis in the Developing Neural Tube, Face, and Limb Bud

Developmental Biology

Tamiko Nishimura¹  Jun Motoyama¹  Kazuhiro Eto¹  Kazushi Aoto¹ 

[1] Molecular Neuropathology Group, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

关键词: GLI3;    FGF8;    SHH;    brain patterning;    optic field;    limb development;    facial malformation;    apoptosis;   

DOI  :  10.1006/dbio.2002.0811

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

ThezincfingertranscriptionfactorGLI3isconsideredarepressorofvertebrateHedgehog(Hh)signaling.Inhumans,theabsenceofGLI3functioncausesGreigcephalopolysyndactylysyndrome,affectingthedevelopmentofthebrain,eye,face,andlimb.Becausetheetiologyofthesemalformationsisnotwellunderstood,weexaminedthephenotypeofmouseGli3−/−mutantsasamodeltoinvestigatethis.Weobservedanup-regulationofFgf8intheanteriorneuralridge,isthmus,eye,facialprimordia,andlimbbudsofmutantembryos,sitescoincidingwiththehumandisease.Intriguingly,endogenousapoptosiswasreducedinFgf8-positiveareasinGli3−/−mutants.SinceSHHisthoughttobeinvolvedinFgf8regulation,wecomparedFgf8expressioninShh−/−andGli3−/−;Shh−/−mutantembryos.WhereasFgf8expressionwasalmostabsentinShh−/−mutants,itwasup-regulatedinGli3−/−;Shh−/−doublemutants,suggestingthatSHHisnotrequiredforFgf8induction,andthatGLI3normallyrepressesFgf8independentlyofSHH.Inthelimbbud,weprovideevidencethatectopicexpressionofGremlininGli3−/−mutantsmightcontributetoadecreaseinapoptosis.Together,ourdatarevealthatGLI3limitsFgf8-expressiondomainsinmultipletissues,throughamechanismthatmayincludetheinductionormaintenanceofapoptosis.

【 授权许可】

Unknown