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.
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.
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
- 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.