Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System 英文参考文献.docVIP

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Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System 英文参考文献.doc

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Forced Notch Signaling Inhibits Commissural Axon Outgrowth in the Developing Chick Central Nerve System 英文参考文献

ForcedNotchSignalingInhibitsCommissuralAxon OutgrowthintheDevelopingChickCentralNerve System MingShi1*.,ZhirongLiu1.,YonggangLv2.,MinhuaZheng3,FangDu1,GangZhao1,YingHuang4 ,Jiayin Chen4,HuaHan3,YuqiangDing4* 1Department ofNeurology,XijingHospital,Fourth MilitaryMedicalUniversity, Xi’an,China, 2DepartmentofVascularandEndocrine Surgery,FirstAffiliatedHospital, Fourth Military Medical University, Xi’an, China, 3Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an, China, 4DepartmentofAnatomyandNeurobiology,TongjiUniversitySchoolofMedicine,Shanghai,China Abstract Background: A collection of in vitro evidence has demonstrated that Notch signaling plays a key role in the growth of neuritesindifferentiatedneurons.However,theeffectsofNotchsignalingonaxonoutgrowthinaninvivoconditionremain largelyunknown. Methodology/PrincipalFindings:Inthisstudy,theneuraltubesofHH10-11chickembryoswereinovoelectroporatedwith variousNotchtransgenesofactivatingorinhibitingNotchsignaling,andthentheireffectsoncommissuralaxonoutgrowth across the floor plate midline in the chick developing central nerve system were investigated. Our results showed that forced expression of Notch intracellular domain, constitutively active form of RBPJ, or full-length Hes1 in the rostral hindbrain, diencephalon and spinal cord at stage HH10-11 significantly inhibited commissural axon outgrowth. On the other hand, inhibition of Notch signaling by ectopically expressing a dominant-negative form of RBPJ promoted commissural axonal growth along the circumferential axis. Further results revealed that these Notch signaling-mediated axon outgrowth defects may be not due to the alteration of axon guidance since commissural axon marker TAG1 was presentintheaxonsinfloorplatemidline,andalsonotresultfromthechangesincellfatedeterminationofcommissural neurons since the expression of postmitotic neuron marker Tuj1 and specific commissural markers TAG1 and Pax7 was unchanged. Co