Shh-Mediated Increase in β-Catenin Levels Maintains Cerebellar Granule Neuron Progenitors in Proliferation
| Autor: | Shyamala Mani, Saranya Radhakrishnan, Narendrakumar Ramanan, Shalini Harkar, Rajit Narayanan Cheramangalam, Samyutha Rajendran |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cerebellum
animal structures 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Downregulation and upregulation Interneurons medicine Animals Hedgehog Proteins Sonic hedgehog Cerebellar Neoplasms Transcription factor Cells Cultured beta Catenin Cell Proliferation 030304 developmental biology Neurons Mice Inbred BALB C 0303 health sciences biology Chemistry Wnt signaling pathway Cell biology medicine.anatomical_structure Neurology Mitogen-activated protein kinase Catenin embryonic structures biology.protein Neurology (clinical) N-Myc 030217 neurology & neurosurgery Medulloblastoma |
| Zdroj: | The Cerebellum. 19:645-664 |
| ISSN: | 1473-4230 1473-4222 |
| DOI: | 10.1007/s12311-020-01138-2 |
| Popis: | Cerebellar granule neuron progenitors (CGNPs) give rise to the cerebellar granule neurons in the developing cerebellum. Generation of large number of these neurons is made possible by the high proliferation rate of CGNPs in the external granule layer (EGL) in the dorsal cerebellum. Here, we show that upregulation of β-catenin can maintain murine CGNPs in a state of proliferation. Further, we show that β-catenin mRNA and protein levels can be regulated by the mitogen Sonic hedgehog (Shh). Shh signaling led to an increase in the level of the transcription factor N-myc. N-myc was found to bind the β-catenin promoter, and the increase in β-catenin mRNA and protein levels could be prevented by blocking N-myc upregulation downstream of Shh signaling. Furthermore, blocking Wingless-type MMTV integration site (Wnt) signaling by Wnt signaling pathway inhibitor Dickkopf 1 (Dkk-1) in the presence of Shh did not prevent the upregulation of β-catenin. We propose that in culture, Shh signaling regulates β-catenin expression through N-myc and results in increased CGNP proliferation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink