Foxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells
作者： Katrina L Adams , David L Rousso , Joy A Umbach , Bennett G Novitch , None
DOI: 10.1038/NCOMMS7778
关键词: Spinal muscular atrophy 、 Neuroscience 、 Spinal cord 、 Embryonic stem cell 、 Amyotrophic lateral sclerosis 、 Cellular differentiation 、 Anatomy 、 Forelimb 、 Axon guidance 、 Stem cell 、 Biology
摘要: Spinal motor neurons (MNs) control diverse tasks including respiration, posture and locomotion that are disrupted by neurodegenerative diseases such as amyotrophic lateral sclerosis spinal muscular atrophy. Methods directing MN differentiation from stem cells have been developed to enable disease modelling in vitro. However, most protocols produce only a limited subset of endogenous subtypes. Here we demonstrate limb-innervating column (LMC) MNs can be efficiently generated mouse human embryonic through manipulation the transcription factor Foxp1. Foxp1-programmed exhibit features medial LMC expression specific pool markers axon guidance receptors. Importantly, they preferentially project axons towards limb muscle explants vitro distal muscles vivo upon transplantation-hallmarks bona fide MNs. These results present an effective approach for generating populations studying development disease.
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