Studes usng Drosopha spermatogeness as a model systemhave showthat multple conserved sgnalng pathways regulate stem cell self renewal and dfferentatothe tests nche.Two populatons of stem cells resde the apex of the Drosopha exams, germlne stem cells whch make sperm, and somatc stem cells knowas cyst stem cells whch develop assistance cells.The two forms of stem cells are anchored all-around a cluster of somatc support cells knowas thehub.Thehub specfcally expresses the secreted glycoproteUpd, whch actvates thehghly conserved Janus Knase Sgnal Transducer and Actvator of Transcrptosgnalng pathway adjacent over here stem cells va the transmembrane receptor Domeless.JAK STAT sgnalng s requred for the mantenance of the two GSCs and CySCs.CySCs, actvatoof JAK STAT sgnalng leads on the expressoof the Stat92E target Znc fngerhomeodoma1, whch shghly expressed CySCs and quckly downregulated cyst cell daughters.Smar to Stat92E, ZFH1 s requred ntrnscally for CySC mantenance,zfh1 or Stat92E mutant CySCs dfferentate wth2 three days.
Furthermore, sustaned actvatoof the JAK STAT sgnalng pathway or ts target zfh1 the CySCs and cyst cells s suffcent to trigger CySC lke cells to accumulate during the exams, far outsde in the ordinary nche regon.A strkng consequence of ths phenotype s the excess CySCs nonautonomously promote the accumulatoof GSCs during the tests.Ths Gefitinib Iressa s impressive consderng that ectopc actvatoof the JAK STAT pathway all through the germlne s not suffcent to prevent dfferentatoof the germ cells.nonetheless, aet undentfed sgnal from CySCs whch actvates the BMpathway neghborng GSCs may possibly be partally responsble for the mantenance of GSCs a GSC lke state.For that reason, the GSC nche s made unot only ofhub cells, but CySCs too.GSCs and CySCs typcally dvde asymmetrcally, this kind of that 1 daughter cell remans adjacent to thehub whe another one will get pushed away from the nche.Snce Upd appears to act more than a short dstance, the GSC and CySC daughters which can be dsplaced from thehub no longer receve the sgnals that specfy stem cell dentty and begto dfferentate.
The gonalblast daughter undergoes four mtotc dvsons wth ncomplete cytokness

resultng 16 nterconnected spermatogona, whch further dfferentate, undergong meoss and spermogeness to form sperm.Cyst cell daughters ext the mtotc cycle, but ncrease sze as they dfferentate.Pars of cyst cells contnue to enveloeach gonalblast and ts descendants all through spermatogeness.fact, encystment within the germlne by the cyst cells s essental for ther proper dfferentaton.Several negatve regulators from the JAK STAT pathwayhave beecharacterzed.These nclude protens in the Suppressor of Cytokne Sgnalng famy,all contaaSH2 domaand a SOCS box, and bnd to phosphorylated tyrosnes oreceptors and or JAKs to attenuate sgnalng by recrutng the proteasomal degradatomachnery to these targets.