Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Sci Rep. 2018 Nov 6;8(1):16410. doi: 10.1038/s41598-018-34745-5.
Mutations in the SALL4 gene cause human syndromes with defects in multiple organs. Sall4 expression declines rapidly in post-gastrulation mouse embryos, and our understanding of the requirement of Sall4 in animal development is still limited. To assess the contributions of Sall4 expressing cells to developing mouse embryos, we monitored temporal changes of the contribution of Sall4 lineages using a Sall4 GFP-CreER knock-in mouse line and recombination-dependent reporter lines. By administering tamoxifen at various time points we observed that the contributions of Sall4 lineages to the axial level were rapidly restricted from the entire body to the posterior part of the body. The contribution to forelimbs, hindlimbs, craniofacial structures and external genitalia also declined after gastrulation with different temporal dynamics. We also detected Sall4 lineage contributions to the extra-embryonic tissues, such as the yolk sac and umbilical cord, in a temporal manner. These Sall4 lineage contributions provide insights into potential roles of Sall4 during mammalian embryonic development. In postnatal males, long-term lineage tracing detected Sall4 lineage contributions to the spermatogonial stem cell pool during spermatogenesis. The Sall4 GFP-CreER line can serve as a tool to monitor spatial-temporal contributions of Sall4 lineages as well as to perform gene manipulations in Sall4-expressing lineages.
SALL4 基因突变会导致人类多种器官缺陷综合征。Sall4 在小鼠胚胎原肠胚后迅速表达下调，而我们对 Sall4 在动物发育中的需求的理解仍然有限。为了评估 Sall4 表达细胞对发育中小鼠胚胎的贡献，我们使用 Sall4 GFP-CreER 敲入小鼠系和依赖重组的报告基因系监测 Sall4 谱系的时间变化。通过在不同时间点给予他莫昔芬，我们观察到 Sall4 谱系对轴向水平的贡献从整个身体迅速局限于身体的后部分。在原肠胚后，Sall4 谱系对前肢、后肢、颅面结构和外生殖器的贡献也以不同的时间动态下降。我们还以时间依赖的方式检测到 Sall4 谱系对卵黄囊和脐带等胚胎外组织的贡献。这些 Sall4 谱系的贡献为 Sall4 在哺乳动物胚胎发育中的潜在作用提供了新的视角。在出生后的雄性中，长期谱系追踪检测到 Sall4 谱系在精子发生过程中对精原干细胞池的贡献。Sall4 GFP-CreER 系可作为一种工具，用于监测 Sall4 谱系的时空贡献，并在 Sall4 表达谱系中进行基因操作。
