DepartmentKidney Development
Publication date5-Nov-2014

Sall4 is Essential for Mouse Primordial Germ Cell Specification by Suppressing Somatic Cell Program Genes
Yasuka L. Yamaguchi, *Satomi S. Tanaka, Maho Kumagai, Yuka Fujimoto, Takeshi Terabayashi, Yasuhisa Matsui and *Ryuichi Nishinakamura (*corresponding authors).
Stem Cells, 2014 (DOI: 10.1002/stem.1853)

The Sall4 zinc finger protein is a critical transcription factor for pluripotency in embryonic stem cells (ESCs). It is also involved in the formation of a variety of organs, in mice and humans. We report the essential roles of Sall4 in mouse primordial germ cell (PGC) specification. PGC specification is accompanied by the activation of the stem cell program and repression of the somatic cell program in progenitor cells. Conditional inactivation of Sall4 during PGC specification led to a reduction in the number of PGCs in embryonic gonads. Sall4del/del PGCs failed to translocate from the mesoderm to the endoderm and underwent apoptosis. In Sall4del/del PGC progenitors, somatic cell program genes (Hoxa1 and Hoxb1) were de-repressed (Figure), while activation of the stem cell program was not impaired. We demonstrated that in differentiated ESCs, Sall4 bound to these somatic cell program gene loci, which are reportedly occupied by Prdm1 in embryonic carcinoma cells. Given that Sall4 and Prdm1 are known to associate with the histone deacetylase repressor complex, our findings suggest that Sall4 suppresses the somatic cell program possibly by recruiting the repressor complex in conjunction with Prdm1; therefore, it is essential for PGC specification.




Figure : Sall4 is required for repression of somatic cell program genes during PGC specification.
(A–C”’) Immunohistochemical analysis showed that Pou5f1-positive PGC progenitors failed to repress Hoxb1 expression. (A) A bright-field image of the E7.0 streak stage embryo (transverse section, posterior to the right). The boxed area in A indicates the position of B–C”’ magnified views. (B, C) Immunostaining for Pou5f1 (green), (B’, C’) Hoxb1 (red), (B”, C”) a merged image, and (B”’, C”’) DAPI nuclear staining (blue).