Ectopic WntBeta–Catenin Signaling Induces Neurogenesis in the Spinal Cord and Hindbrain Floor Plate 英文参考文献.docVIP
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Ectopic WntBeta–Catenin Signaling Induces Neurogenesis in the Spinal Cord and Hindbrain Floor Plate 英文参考文献
EctopicWnt/Beta–CateninSignalingInduces
NeurogenesisintheSpinalCordandHindbrainFloor
Plate
MilanJoksimovic1¤,MeeraPatel1,MakotoMarkTaketo2,RandyJohnson3,RajeshwarAwatramani1*
1DepartmentofNeurologyandCenterforGeneticMedicine,FeinbergMedicalSchool,NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica,2Department
of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe′-cho, Sakyo, Kyoto, Japan, 3Department of Biochemistry and Molecular Biology,
UniversityofTexas,M.D.AndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica
Abstract
The most ventral structure of the developing neural tube, the floor plate (FP), differs in neurogenic capacity along the
neuraxis. The FP is largely non-neurogenic at the hindbrain and spinal cord levels, but generates large numbers of
dopamine(mDA)neuronsatthemidbrainlevels.Wnt1,andotherWntsareexpressedintheventralmidbrain,andWnt/beta
cateninsignalingcanatleastinpartaccount forthedifferenceinneurogeniccapacityoftheFPbetween midbrainand
hindbrain levels. To further develop the hypothesis that canonical Wnt signaling promotes mDA specification and FP
neurogenesis, we have generated a model wherein beta–catenin is conditionally stabilized throughout the FP. Here, we
unambiguouslyshowbyfatemappingFPcellsinthismutant,thatthehindbrainandspinalcordFParerenderedhighly
neurogenic,producinglargenumbersofneurons.WerevealthataneurogenichindbrainFPresultsinthealteredsettling
pattern of neighboring precerebellar neuronal clusters. Moreover, in this mutant, mDA progenitor markers are induced
throughouttherostrocaudalaxisofthehindbrainFP,althoughTH+mDAneuronsareproducedonlyintherostralaspectof
rhombomere (r)1. This is, at least in part, due to depressed Lmx1b levels by Wnt/beta catenin signaling; indeed, when
Lmx1blevelsarerestoredinthismutant,mDAareobservednotonlyinrostralr1,butalsoatmorecaudalaxiallevelsinthe
hindbrain,butnotinthespinalcord. Takentogether,thesedataelucidatebothpatterningandneurogenicfunctionsof
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