Regulation of human neural progenitor cell proliferation by Ryk-mediated Wnt signaling
Human ES cells can be used to make healthy neurons to replace the cells that are lost in neurological diseases such as Alzheimer’s and Parkinson’s diseases. This holds great hope for future treatment of these disorders. Our research aims to produce neurons from ES cells more efficiently. During the process of differentiation to form nerve cells, human ES cells first develop into primitive neural progenitor cells before they become mature functional neurons. Our research focuses on how we can expand the neural progenitor cell population.
We have found that a cell surface protein called Wnt can expand neural progenitor cells. However, it is not clear how this protein can make human neural progenitor cells grow. This proposal will address the question. We will determine which surface molecules can recognize Wnt and how these signals control cell growth. This proposed research will help us to find a method to expand neural progenitor cells and thus make more neurons in the future. This will eventually contribute to the clinical application of human embryonic stem cells in the treatment of neurological diseases.
Neurodegenerative diseases, such as Alzheimer’s and Parkinson diseases, and neuronal injuries caused by stroke and trauma, will result in neuronal cell loss. Current treatments cannot replace or recover the neuronal loss. Our proposed research ultimately may lead to the development of an effective treatment for the neuronal cell loss. Once we find a detailed Wnt pathway to control neural progenitor cell expansion, there will be many possible clinical applications. Transplant-ready neuronal tissues, gene therapy, and drugs targeting the Wnt pathway to promote neuronal regeneration are some of the treatments of the future for neurological disorders. Our finding will facilitate the progress of developing those new, promising treatments. The success of our project in neural progenitor cells expansion will greatly improve the quality of health for Californians.
The grant investigates to grow human neural progenitor cells by manipulating Ryk-mediated Wnt signaling. We discovered that Ryk signaling regulates neurogenesis and cleavage of Ryk is important for this processes.
Neurodegenerative diseases such as Alzheimer’s and Parkinson, as well as neuronal injuries caused by stroke or trauma, result in neuronal cell loss. Current treatments cannot replace or repair the damaged cells. Our proposed research may ultimately lead to the development of an effective treatment for neuronal cell loss.
We have set up an effective system for growing neural progenitor cells derived from human ES cells. We have performed experiments aimed at expanding neural stem cell populations and growing neurons. This could lead to many possible clinical applications.
Transplant-ready neuronal tissues, gene therapies, and drugs targeting the Wnt pathway in order to promote neuronal regeneration are some of the treatments for neurological disorders that may be possible in the future. Our findings will facilitate the progress of developing these new, promising treatments. The success of our project in neural progenitor cell expansion could greatly improve the quality of life for Californians and people everywhere.
- PLoS One (2013) Functional impacts of NRXN1 knockdown on neurodevelopment in stem cell models. (PubMed: 23536886)
- Hum Mol Genet (2013) The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells. (PubMed: 23710042)
- Stem Cell Res Ther (2012) The gene expression profiles of induced pluripotent stem cells from individuals with childhood cerebral adrenoleukodystrophy are consistent with proposed mechanisms of pathogenesis. (PubMed: 23036268)
- J Biol Chem (2009) Cdc37 regulates Ryk signaling by stabilizing the cleaved Ryk intracellular domain. (PubMed: 19269974)