Forward genetics uncovers Transmembrane protein 107 as a novel factor required for ciliogenesis and Sonic hedgehog signaling ☆

Developmental Biology

Scott D. Weatherbee²  Baolin Wang³  Yong Kong¹  Kasey J. Christopher² 

[1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USAW.M. Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT 06520, USA;Department of Genetics, Yale University, New Haven, CT 06520, USA;Department of Genetics, Weill Medical College of Cornell University, New York, NY 10021, USA

DOI  :  10.1016/j.ydbio.2012.06.008

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Ciliaaredynamicorganellesthatareessentialforavastarrayofdevelopmentalpatterningevents,includingleft-rightspecification,skeletalformation,neuraldevelopment,andorganogenesis.Despiterecentadvancesinunderstandingciliaformandfunction,manykeyciliogenesiscomponentshaveyettobeidentified.Byusingaforwardgeneticsapproach,weisolatedanovelmutantallele(schlei)ofthemouseTransmembraneprotein107(Tmem107)gene,whichweshowhereiscriticalforciliaformationandembryonicpatterning.Tmem107isrequiredfornormalSonichedgehog(Shh)signalingintheneuraltubeandactsincombinationwithGli2andGli3topatternventralandintermediateneuronalcelltypes.schleimutantsalsoformextradigits,andwedemonstratethatTmem107actsintheShhpathwaytodeterminedigitnumber,butnotidentity,byregulatingasubsetofShhtargetgenes.Phenotypically,schleimutantsshareseveralfeatureswithotherciliamutants;however,spatialrestrictionofmutantphenotypesandlackofleft-rightpatterningdefectsinschleianimalssuggestdifferentialrequirementsforTmem107inciliaformationindistincttissues.Also,incontrasttomutantswithcompletelossofcilia,schleimutantsretainsomefunctionofbothGliactivatorandrepressorforms.Together,thesestudiesidentifyapreviouslyunknownregulatorofciliogenesisandprovideinsightintohowciliaryfactorsaffectShhsignalingandciliabiogenesisindistincttissues.

【 授权许可】

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