Two human syndromes are associated with mutations in SALL genes. The autosomal dominant inherited is caused by mutations in the SALL1 gene and mutations in the SALL4 gene have been found in , acro-renal-ocular and IVIC syndrome. In mice four Sall family members exist and gene disruption studies have demonstrated that their products are essential at various steps of mammalian development.
We and others have shown that gene disruption of SALL4, the earliest expressed member of the SALL family, leads to peri-implantation lethality and neither embryonic stem (ES) cells nor extra embryonic endoderm (XEN) cells can be derived from SALL4 null blastocysts ().
Interestingly, SALL4 regulates different transcriptional programs in ES and XEN cells. How SALL4 is able to do so has, so far, remained elusive. Studies in ES cells have demonstrated that SALL4 expression is transcriptionally regulated by OCT4, SOX2 and Nanog and consistent with this observation SALL4 is down-regulated upon retinoic acid induced differentiation of ES cells. Furthermore, based on indirect evidence SALL4 has been positioned in the center of a protein interaction network underlying pluripotency of ES cells.