Developmental Changes in Notch1 and Numb Expression Mediated by Local Cell–Cell Interactions Underlie Progressively Increasing Delta Sensitivity in Neural Crest Stem Cells

[摘要] Neuralstemcellsbecomeprogressivelylessneurogenicandmoregliogenicwithdevelopment.Here,weshowthatbetweenE10.5andE14.5,neuralcreststemcells(NCSCs)becomeincreasinglysensitivetotheNotchligandDelta-Fc,aprogliogenicandanti-neurogenicsignal.Thistransitioniscorrelatedwitha20-to30-foldincreaseintherelativeratioofexpressionofNotchandNumb(aputativeinhibitorofNotchsignaling).MisexpressionexperimentssuggestthatthesechangescontributecausallytoincreasedDeltasensitivity.Moreover,suchchangescanoccurinNCSCsculturedatclonaldensityintheabsenceofothercelltypes.However,theyrequirelocalcell–cellinteractionswithindevelopingclones.Delta-Fcmimicstheeffectofsuchcell–cellinteractionstoincreaseNotchanddecreaseNumbexpressioninisolatedNCSCs.Thus,Delta-mediatedfeedbackinteractionsbetweenNCSCs,coupledwithpositivefeedbackcontrolofNotchsensitivitywithinindividualcells,mayunderliedevelopmentalchangesintheligand-sensitivityofthesecells.

[学科分类] 生物科学（综合）

[关键词] Numb;Notch;BMP;Delta;neurogenesis;neural stem cells