Method for Efficient Generation of Neurons from Non-Neuronal Cells

Technology #18150

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Diagram of the MSaa embryonic lineage, which gives rise to the I4 neuron. Neuronal cells are shown in blue, and muscle and other mesodermal cells are shown in red. The I4 neuron is generated by a mother cell that divides to generate the I4 neuron and the pharyngeal muscle cell pm5.The hlh-3 mutant I4 cell adopts the pharyngeal muscle cell fate of its sister pm5. The mutant I4 cell expressed a pm5-specific reporter Pace-1::mCherry as well as pharyngeal muscle reporters Pmyo-2::mCherry::H2B and ceh-22::mCherry, none of which was expressed in wild-type I4 (boxes and insets).
Professor Robert Horvitz
Department of Biology, MIT
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Shuo Luo
Department of Biology, MIT
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Michelle Hunt
MIT Technology Licensing Officer
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Method for Efficient Generation of Neurons from Non-Neuronal Cells

PCT Patent Application Filed


This technology can be applied to the study and treatment of neurodegenerative diseases and may be used by pharmaceutical or stem cell/regenerative medicine companies.

Problem Addressed

The production of neurons from non-neural cells is an integral aspect of the modeling and development of therapies for neurodegenerative diseases. Current methods of generating neurons from non‑neuronal cells are inefficient and have an efficacy rate of less than 20%. This technology employed a novel assay to identify genes needed for highly efficient neurogenesis in C. elegans and provides suggested uses of these genes and their mammalian analogs for study and treatment of diseases in the human nervous system.


The C. elegans nervous system contains a few neurons that are derived highly efficiently (100% of time) from muscle lineages.  We developed a novel assay to identify genes that are required to generate one such neuron, I4, the mother of which divides to generate the I4 neuron and a muscle cell.  Analysis of the mutants in which the I4 cell adopts a muscle-like cell fate has led to the identification of two pathways that cooperate to promote robust I4 neurogenesis from mesoderm. These pathways include proneural and mediator proteins, some of which were not previously suspected to be involved in efficient neuronal reprogramming. The genes identified by this novel assay have human counterparts likely to be useful in promoting the transdifferentiation of non-neuronal human cells into neurons, with important implications for the study and treatment of human disorders of the nervous system.


  • Insights into I4 development allow a more complete understanding of neurogenesis from mesoderm.
  • Genes identified have mammalian counterparts and therefore might be useful in the study of the human nervous system and its pathology as well as in developing novel methods for therapeutic treatments.