Ryk, a receptor regulating Wnt5a-mediated neurogenesis and axon morphogenesis of ventral midbrain dopaminergic neurons
| Autor: | Chathurini V. Fernando, Steven A. Stacker, R. Jeroen Pasterkamp, Christopher R. Bye, Maria L Macheda, Clare L. Parish, Asheeta A. Prasad, Brette Blakely |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Neurogenesis Biology Receptor tyrosine kinase Wnt-5a Protein Rats Sprague-Dawley Tissue Culture Techniques Mice Prosencephalon Neural Stem Cells Dopamine Mesencephalon Internal medicine medicine Morphogenesis Animals Humans Receptor Mice Knockout Dopaminergic Neurons Dopaminergic Wnt signaling pathway Gene Expression Regulation Developmental Receptor Protein-Tyrosine Kinases Cell Biology Hematology Neural stem cell Axons Cell biology Rats Transplantation Wnt Proteins Endocrinology HEK293 Cells biology.protein Developmental Biology medicine.drug |
| Zdroj: | Stem cells and development. 22(15) |
| ISSN: | 1557-8534 |
| Popis: | Ryk is an atypical transmembrane receptor tyrosine kinase that has been shown to play multiple roles in development through the modulation of Wnt signaling. Within the developing ventral midbrain (VM), Wnts have been shown to contribute to the proliferation, differentiation, and connectivity of dopamine (DA) neurons; however, the Wnt-related receptors regulating these events remain less well described. In light of the established roles of Wnt5a in dopaminergic development (regulating DA differentiation as well as axonal growth and repulsion), and its interaction with Ryk elsewhere within the central nervous system, we investigated the potential role of Ryk in VM development. Here we show temporal and spatial expression of Ryk within the VM, suggestive of a role in DA neurogenesis and axonal plasticity. In VM primary cultures, we show that the effects of Wnt5a on VM progenitor proliferation, DA differentiation, and DA axonal connectivity can be inhibited using an Ryk-blocking antibody. In support, Ryk knockout mice showed reduced VM progenitors and DA precursor populations, resulting in a significant decrease in DA cells. However, Ryk(-/-) mice displayed no defects in DA axonal growth, guidance, or fasciculation of the MFB, suggesting other receptors may be involved and/or compensate for the loss of this receptor. These findings identify for the first time Ryk as an important receptor for midbrain DA development. |
| Databáze: | OpenAIRE |
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