Development of neural tube has been extensively modeled in vitro using human pluripotent stem cells (hPSCs) that are able to form radially organized cellular structures called neural rosettes. While a great amount of research has been done using neural rosettes, studies have only inadequately addressed how rosettes are formed and what the molecular mechanisms and pathways involved in their formation are. Here we address this question by detailed analysis of the expression of pluripotency and differentiation-associated proteins during the early onset of differentiation of hPSCs towards neural rosettes. Additionally, we show that the BMP signaling is likely contributing to the formation of the complex cluster of neural rosettes and its inhibition leads to the altered expression of PAX6, SOX2 and SOX1 proteins and the rosette morphology. Finally, we provide evidence that the mechanism of neural rosettes formation in vitro is reminiscent of the process of secondary neurulation rather than that of primary neurulation in vivo. Since secondary neurulation is a largely unexplored process, its understanding will ultimately assist the development of methods to prevent caudal neural tube defects in humans.
- MeSH
- buněčná diferenciace * MeSH
- COUP transkripční faktor II genetika metabolismus MeSH
- faktory domény POU genetika metabolismus MeSH
- homeodoménové proteiny genetika metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nervové kmenové buňky cytologie metabolismus MeSH
- neurální trubice cytologie embryologie metabolismus MeSH
- neurulace * MeSH
- pluripotentní kmenové buňky cytologie metabolismus MeSH
- transkripční faktor PAX6 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH