WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

• Published in: Development (Cambridge)
• Main Authors: Gomez, Gustavo A., Prasad, Maneeshi S., Wong, Man, Charney, Rebekah M., Shelar, Patrick B., Sandhu, Nabjot, Hackland, James O. S., Hernandez, Jacqueline C., Leung, Alan W., García-Castro, Martín I.
• Format: Journal Article
• Language: English
• Published: 01-01-2019
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.175604

WNT/β-CATENIN signaling is critical for neural crest (NC) formation, yet magnitude effects of the signal remain ill-defined. Using a robust model of human NC formation based on human pluripotent stem cells (hPSCs), we expose that the WNT signal modulates the axial identity of NCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX- NC, and high WNT leading to posterior OTX-, HOX+ NC. Differentiation tests of posterior NC confirm expected derivatives including posterior specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC exhibit a transient TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, which suggest a critical role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected Retinoic Acid (RA) and FGF are able to modulate HOX expression in the posterior NC. Surprisingly, early RA supplementation prohibits NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.