アクティブボード・２００７年　７月
　　　　　・・・・・２００７年　７月　２日更新・・・・・

研究発表を行った学会；
・第４０回日本発生生物学会・第５９回日本細胞生物学会　合同大会、2007年 5月28~30日(福岡)

タイトル；Sall4 permissively maintains stemness of embryonic stem cells.
発表者；　由利　俊祐　氏
　　　（熊本大学　発生医学研究センター　細胞識別分野）
Abstract；
Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. Sall4-null mouse leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation, when cultured on feeder cells (Sakaki-Yumoto et al., Development 2006). These Sall4-null ES cells predominantly populated the inner cell mass when aggregated with 8-cell stage embryos. Further, Sall4-null blastocysts before implantation (E3.5) showed no aberrant differentiation, suggesting that Sall4 is not essential for the initial commitment of the inner cell mass and the trophectoderm. However, in the absence of feeder cells, some of Sall4-null ES cells differentiated spontaneously and expressed Cdx2, a trophectoderm marker, while the other cells were maintained in an undifferentiated state with unaltered Oct3/4 expression. Embryoid bodies derived from Sall4-null ES cell expressed higher level of Cdx2 and other trophectoderm markers, as compared to heterozygous cells. Thus Sall4 may play a permissive role in the maintenance of stemness of ES cells, and Sall4 absence could gradually result in differentiation into extraembryonic cell lineage. To address whether Sall4 is involved in keeping stemness in vivo at post-implantation, we recently generated epiblast-specific Sall4 knockout mice, as ES cells contribute to epiblast when injected into blasotocysts. These mice showed abnormal development of allantois and somites, and lineage commitment of the epiblast in Sall4 absence will be presented. As Sall4 reportedly binds to Oct3/4 and Nanog, we will also discuss the potential molecular mechanisms of Sall4 in ES cells.