第十一章 细胞分化与干细胞-zsy新.ppt

从种系的发生来看，专司生殖功能的性细胞（germline）从体细胞（somaticcell）分化出来，被认为是后生生物起源的重要标志，并且随着进化水平的提高，生殖细胞的分化程度也呈现不断提高的趋势。Differentiationofovariesandtestesfrombipotentialgonads*从种系的发生来看，专司生殖功能的性细胞（germline）从体细胞（somaticcell）分化出来，被认为是后生生物起源的重要标志，并且随着进化水平的提高，生殖细胞的分化程度也呈现不断提高的趋势。Differentiationofovariesandtestesfrombipotentialgonads*在性腺早期分化过程中，FGF9、SRY和sox9构成了一个调控网络：SRY的表达，启动了sox9的表达，而sox9作为转录因子，激活FGF9；FGF9蛋白分泌到细胞外，作为信号分子，起两方面的作用：一是通过信号转导过程作用于本身的sox9基因，维持其表达，同时也作用于邻近细胞，使前体细胞向睾丸支持细胞分化过程中sox9的表达水平保持相对平衡，保证分化的同步。/doi/10.1002/wdev.42/fullFigure1.Modelofgeneregulatorynetworksinmammaliansexdetermination.Sex-determininggeneticactivityintheXYpre-Sertolicell(PSC)isdominatedbySRY-SOX9-FGF9/FGFR2.Thisgeneticpathwayisstabilizedbymutuallypositive(curvedarrows)interactionsbetweenSOX9andFGF9,resultingincontinuedexpressionofSOX9intheSertolicelllineage,incombinationwithantagonism(hammeredlines)ofovary-determininggenes/proteins(showninred).OnlyashortperiodofSRYexpressionisrequiredtoupregulateSox9fromitsbasallevelsinthebipotentialgonad.FGF9andPGD2supportparacrinesignaling(arrowsexitingfromlowercell),resultingintherecruitmentofadditionalsupportingcellprecursors(upperPSC)thatexpressSRYand/orSOX9totheSertolicelllineage.ThesecretedmoleculesFGF9anddeserthedgehog(DHH)alsofunctioninmasculinizingthegermcellandsteroidogeniccelllineages,respectively.Thistestis-determininggeneregulatorynetworkanditsdownstreamtargets(‘testisgenes’)initiateavarietyofmorphogeneticprocesses,includingthemigrationofendothelialcellsfromtheadjacentmesonephros,whicharecrucialtotheformationoftestiscordsandtheassociatedcoelomicbloodvessel.Inthefemale(XX)gonad,theabsenceofSRYinpregranulosacells(PGC)resultsinsuccessfulantagonismofSOX9/FGF9byovary-determininggeneproducts.Thiscausescommitmenttothegranulosacelllineagean