Open AccessSall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos
Author(s) -
Naoyuki Tahara,
Hiroko Kawakami,
Katherine Q. Chen,
Aaron Anderson,
Malina Yamashita Peterson,
Wuming Gong,
Pruthvi Shah,
S. Hayashi,
Ryuichi Nishinakamura,
Yasushi Nakagawa,
Daniel J. Garry,
Yasuhiko Kawakami
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.177659
Subject(s) - biology , embryo , microbiology and biotechnology , elongation , genetics , embryogenesis , progenitor cell , evolutionary biology , stem cell , materials science , metallurgy , ultimate tensile strength
Bi-potential neuromesodermal progenitors (NMPs) produce both neural and paraxial mesodermal progenitors in the trunk and tail during vertebrate body elongation. We show that Sall4, a pluripotency-related transcription factor gene, has multiple roles in regulating NMPs and their descendants in post-gastrulation mouse embryos. Sall4 deletion using TCre caused body/tail truncation, reminiscent of early depletion of NMPs, suggesting its role in NMP maintenance. This phenotype became significant at the time of the trunk to tail transition, suggesting that Sall4 maintenance of NMPs enables tail formation. Sall4 mutants exhibit expanded neural and reduced mesodermal tissues, indicating its role in NMP differentiation balance. Mechanistically, we show that Sall4 promotion of WNT/ß-catenin signaling contributes to NMP maintenance and differentiation balance. RNA-Seq and SALL4 ChIP-Seq analyses support the notion that Sall4 regulates both mesodermal and neural development. Furthermore, in the mesodermal compartment, genes regulating presomitic mesoderm differentiation are downregulated in Sall4 mutants. In the neural compartment, we show that differentiation of NMPs towards post-mitotic neuron is accelerated in Sall4 mutants. Our results collectively provide evidence supporting the role of Sall4 in regulating NMPs and their descendants.