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-CreERT2 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-CreERT2 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.
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We are grateful to Katherine Chen, Jennifer Kim and Malina Yamashita Peterson for their excellent technical assistance. We are also grateful Drs. Juan Carlos Izpisúa Belmonte, Daniel J. Garry, Yasushi Nakagawa, Ryuichi Nishinakamura, Michael O’Connor and Jop van Berlo for sharing materials and equipment, and to Dr. Andrew McMahon for the GCE cassette. This study was supported by grants from the National Institute of Arthritis, Musculoskeletal and Skin Diseases to YK (R01AR064195) and the National Institute of General Medical Sciences to DZ (R01GM059152). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.