TY - JOUR
T1 - Sall4 regulates neuromesodermal progenitors and their descendants during body elongation in mouse embryos
AU - Tahara, Naoyuki
AU - Kawakami, Hiroko
AU - Chen, Katherine Q.
AU - Anderson, Aaron
AU - Yamashita Peterson, Malina
AU - Gong, Wuming
AU - Shah, Pruthvi
AU - Hayashi, Shinichi
AU - Nishinakamura, Ryuichi
AU - Nakagawa, Yasushi
AU - Garry, Daniel J.
AU - Kawakami, Yasuhiko
N1 - Publisher Copyright:
© 2019. Published by The Company of Biologists Ltd.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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 a role of Sall4 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 a role of Sall4 in NMP differentiation balance. Mechanistically, we show that Sall4 promotion of WNT/β-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.
AB - 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 a role of Sall4 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 a role of Sall4 in NMP differentiation balance. Mechanistically, we show that Sall4 promotion of WNT/β-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.
KW - Body/tail elongation
KW - Mesodermal progenitors
KW - Neural progenitors
KW - Neuromesodermal progenitors
KW - Sall4
KW - WNT/β-catenin signaling
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U2 - 10.1242/DEV.177659
DO - 10.1242/DEV.177659
M3 - Article
C2 - 31235634
AN - SCOPUS:85069949794
SN - 0950-1991
VL - 146
JO - Development (Cambridge)
JF - Development (Cambridge)
IS - 14
M1 - dev177659
ER -