EGFR Signaling Termination via Numb Trafficking in Ependymal Progenitors Controls Postnatal Neurogenic Niche Differentiation
| Autor: | Joon Pyun, Emre Kiziltug, Angelica Ahrens, Khadar Abdi, Chay T. Kuo, Gabriel Neves |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Ependymal Cell Neurogenesis Endocytic cycle Down-Regulation Nerve Tissue Proteins Biology Article General Biochemistry Genetics and Molecular Biology Madin Darby Canine Kidney Cells 03 medical and health sciences Dogs 0302 clinical medicine Neural Stem Cells Ependyma Animals Humans Phosphorylation Stem Cell Niche Progenitor cell Receptor lcsh:QH301-705.5 Mice Knockout Epidermal Growth Factor Membrane Proteins Signal transducing adaptor protein Endocytosis Neural stem cell Cell biology ErbB Receptors Protein Transport HEK293 Cells 030104 developmental biology Animals Newborn lcsh:Biology (General) Mutation NUMB Neuroglia 030217 neurology & neurosurgery Signal Transduction Adult stem cell |
| Zdroj: | Cell Reports, Vol 28, Iss 8, Pp 2012-2022.e4 (2019) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Specialized microenvironments, called niches, control adult stem cell proliferation and differentiation. The brain lateral ventricular (LV) neurogenic niche is generated from distinct postnatal radial glial progenitors (pRGPs), giving rise to adult neural stem cells (NSCs) and niche ependymal cells (ECs). Cellular-intrinsic programs govern stem versus supporting cell maturation during adult niche assembly, but how they are differentially initiated within a similar microenvironment remains unknown. Using chemical approaches, we discovered that EGFR signaling powerfully inhibits EC differentiation by suppressing multiciliogenesis. We found that EC pRGPs actively terminated EGF activation through receptor redistribution away from CSF-contacting apical domains and that randomized EGFR membrane targeting blocked EC differentiation. Mechanistically, we uncovered spatiotemporal interactions between EGFR and endocytic adaptor protein Numb. Ca2+-dependent basolateral targeting of Numb is necessary and sufficient for proper EGFR redistribution. These results reveal a previously unknown cellular mechanism for neighboring progenitors to differentially engage environmental signals, initiating adult stem cell niche assembly. Graphical Abstract In Brief Constructing adult stem niches from postnatal progenitors requires differential cellular interpretations of similar microenvironmental signals. Abdi et al. show that in an EGF-rich environment needed for adult neural stem cell proliferation, a subpopulation of postnatal progenitors downregulates EGFR signaling via targeted receptor trafficking, promoting multiciliated ependymal niche cell differentiation. |
| Databáze: | OpenAIRE |
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