RESUMO
In the developing spinal cord, signals of the roof plate pattern the dorsal progenitor domain and control the specification of three neuron types, dorsal interneurons dI1, dI2, and dI3. Bmp and Wnt/beta-catenin signals as well as transcription factors like Olig3 or Ngn1/2 are essential in this process. We have studied the epistatic relationship between Bmp and Wnt/beta-catenin signals and the transcription factor Olig3 in dorsal spinal cord patterning. Using beta-catenin gain-of-function and compound beta-catenin gain-of-function/Olig3 loss-of-function mutations in mice, we could show that Wnt/beta-catenin signals act upstream of Olig3 in the specification of dI2 and dI3 neurons. The analysis of such compound mutant mice allowed us to distinguish between the two functions of Wnt/beta-catenin signaling in proliferation and patterning of dorsal progenitors. Using electroporation of chick spinal cords, we further demonstrate that Bmp signals act upstream of Wnt/beta-catenin in the regulation of Olig3 and that Wnt/beta-catenin signals play an instructive role in controlling Olig3 expression. We conclude that Wnt/beta-catenin and BMP signals coordinately control the specification of dorsal neurons in the spinal cord.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese/fisiologia , Neurônios/citologia , Transdução de Sinais/fisiologia , Medula Espinal/embriologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Embrião de Galinha , Eletroporação , Epistasia Genética , Imunofluorescência , Hibridização In Situ , Camundongos , Mutação/genética , Medula Espinal/citologia , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMO
beta-Catenin is an essential component of the canonical Wnt signaling system that controls decisive steps in development. We employed here two conditional beta-catenin mutant alleles to alter beta-catenin signaling in the central nervous system of mice: one allele to ablate beta-catenin and the second allele to express a constitutively active beta-catenin. The tissue mass of the spinal cord and brain is reduced after ablation of beta-catenin, and the neuronal precursor population is not maintained. In contrast, the spinal cord and brain of mice that express activated beta-catenin is much enlarged in mass, and the neuronal precursor population is increased in size. beta-Catenin signals are thus essential for the maintenance of proliferation of neuronal progenitors, controlling the size of the progenitor pool, and impinging on the decision of neuronal progenitors to proliferate or to differentiate.