Regulation of the Development of Human Neurons by Substratum Elasticity

Abstract

Growth cones, the sensory tips of developing axons, respond to molecular cues present in the environment. Additionally, recent studies suggest local differences in environmental rigidity affect axon development via mechanosensitive protein regulation in growth cones, and is dependent upon neuronal subtype. Neurites innervating the Central Nervous System (CNS) grow more rapidly on flexible substrata. Conversely, neurites projecting into the Peripheral Nervous System (PNS) prefer rigid substrata. By using human forebrain (hFBs) and motor neurons (hMNs) differentiated from Induced Pluripotent Stem Cells (IPSCs), we compared growth rates and morphology of CNS and PNS neurons on varying substrata stiffnesses. We found MNs prefer more rigid substrata, while forebrain neurons do not have a strong preference for rigidity. Finally, we found both hFBs and hMNs express mechanosensitive ion channels. Future studies should investigate differential expression patterns of these ion channels on different rigidities as a possible mechanism for the differential growth we observed.Support or Funding InformationNIH RO1NS41564‐10 (to T.M.G)NIH T32GM007507 (to UW‐NTP)IBS‐SRP at UW‐Madison (NSF grant NSF‐DBI 1063085)NIH‐NIGMS R25GM096955 (to Edu B. Suarez‐Martinez)