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Sall4 regulates posterior trunk mesoderm development by promoting mesodermal gene expression and repressing neural genes in the mesoderm.

Authors :
Pappas, Matthew P.
Hiroko Kawakami
Corcoran, Dylan
Chen, Katherine Q.
Scott, Earl Parker
Wong, Julia
Gearhart, Micah D.
Ryuichi Nishinakamura
Yasushi Nakagawa
Yasuhiko Kawakami
Source :
Development (09501991). Mar2024, Vol. 151 Issue 5, p1-14. 14p.
Publication Year :
2024

Abstract

The trunk axial skeleton develops from paraxial mesoderm cells. Our recent study demonstrated that conditional knockout of the stem cell factor Sall4 in mice by TCre caused tail truncation and a disorganized axial skeleton posterior to the lumbar level. Based on this phenotype, we hypothesized that, in addition to the previously reported role of Sall4 in neuromesodermal progenitors, Sall4 is involved in the development of the paraxial mesoderm tissue. Analysis of gene expression and SALL4 binding suggests that Sall4 directly or indirectly regulates genes involved in presomitic mesoderm differentiation, somite formation and somite differentiation. Furthermore, ATAC-seq in TCre; Sall4 mutant posterior trunk mesoderm shows that Sall4 knockout reduces chromatin accessibility. We found that Sall4-dependent open chromatin status drives activation and repression of WNT signaling activators and repressors, respectively, to promote WNT signaling. Moreover, footprinting analysis of ATAC-seq data suggests that Sall4-dependent chromatin accessibility facilitates CTCF binding, which contributes to the repression of neural genes within themesoderm. This study unveils multiple mechanisms by which Sall4 regulates paraxial mesoderm development by directing activation of mesodermal genes and repression of neural genes. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09501991
Volume :
151
Issue :
5
Database :
Academic Search Index
Journal :
Development (09501991)
Publication Type :
Academic Journal
Accession number :
176156348
Full Text :
https://doi.org/10.1242/dev.202649