Open AccessA novel self-organizing embryonic stem cell system reveals signaling logic underlying the patterning of human ectoderm
Author(s) -
George Britton,
Idse Heemskerk,
Rachel Hodge,
Amina A. Qutub,
Aryeh Warmflash
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.179093
Subject(s) - ectoderm , biology , wnt signaling pathway , embryonic stem cell , microbiology and biotechnology , stem cell , cellular differentiation , neuroscience , anatomy , embryogenesis , signal transduction , embryo , genetics , gene
During development, the ectoderm is patterned by a combination of BMP and WNT signaling. Research in model organisms has provided substantial insight into this process, however, there are currently no systems to study ectodermal patterning in humans. Further, the complexity of neural plate border specification has made it difficult to transition from discovering the genes involved to deeper mechanistic understanding. Here, we develop an in vitro model of human ectodermal patterning, in which hESCs self-organize to form robust and quantitatively reproducible patterns corresponding to the complete medial-lateral axis of the embryonic ectoderm. Using this platform, we show that the duration of endogenous WNT signaling is a crucial control parameter, and that cells sense relative levels of BMP and WNT signaling in making fate decisions. These insights allowed us to develop an improved protocol for placodal differentiation. Thus, our platform is a powerful tool for studying human ectoderm patterning and for improving directed differentiation protocols.