Characterization of axon formation in the embryonic stem cell-derived motoneuron.
The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived  motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1,  vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of  the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore  the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Hung-Chuan
HC
Pan
Ya-Ting
YT
Wu
Shih-Cheng
SC
Shen
Chi-Chung
CC
Wang
Ming-Shiun
MS
Tsai
Fu-Chou
FC
Cheng
Shinn-Zong
SZ
Lin
Ching-Wen
CW
Chen
Ching-San
CS
Liu
Hong-Lin
HL
Su
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000166:cytology