Stem cell therapies have long-since been a promising approach for treating neurodegenerative diseases, but the complexities of the different types and functions of nerve cells continue to pose substantial challenges. The limb-innervating motor neurons (MN) of the lateral motor column (LMC), which control movement of arms and legs, and are often the first to degenerate in ALS, have proven to be particularly difficult to properly replicate. Previous research from Bennett Novitch’s laboratory at the University of California, Los Angeles has shown that the key may lie in the transcription factor forkhead box protein P1 (Foxp1). Foxp1 is necessary for generation of limb-innervating MNs but is rarely expressed in motor neurons derived from stem cells in the lab (see Aug 2002 news story). In a publication in the 14 April Nature Communications, first author Katrina Adams and colleagues demonstrate that expression of Foxp1 in mouse and human embryonic stem cells drives stem cell-derived MNs toward an LMC identity. The Foxp1-differentiated MNs express molecular markers of LMC neurons, and project to distal limb muscles following transplantation into developing chick embryos. Next, the researchers plan to investigate how these MNs identify their specific target muscles and whether they can be used therapeutically.
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Adams KL, Rousso DL, Umbach JA, Novitch BG. Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells. Nat Commun. 2015 Apr 14; 6:6778. Pubmed.