Fate Mapping of Gallbladder Progenitors in Posteroventral Foregut

In early embryogenesis, the posteroventral foregut endoderm gives rise 22 to the budding endodermal organs including the liver, ventral pancreas and gallbladder 23 during early somitogenesis. Despite the detailed fate maps of the liver and pancreatic 24 progenitors in the mouse foregut endoderm, the exact location of the gallbladder 25 progenitors remains unclear. In this study, we performed a DiI fate-mapping analysis 26 using whole-embryo cultures of mouse early somite-stage embryos. Here, we show that 27 the majority of gallbladder progenitors in 9-11-somite-stage embryos are located in the 28 lateral-most domain of the foregut endoderm at the first intersomite junction level along 29 the anteroposterior axis. This definition of their location highlights a novel entry point 30 to understanding of the molecular mechanisms of initial specification of the gallbladder. 31 32 KEY WORDS: fate mapping, foregut, gallbladder, mouse. 33 34-3-34 In mouse early embryogenesis, the foregut endoderm first arises at the early to mid-35 streak stages, leading to the formation of one endodermal sheet layer. The foregut 36 endoderm sheet covers the anterior surface of the embryonic region by the early head 37 fold stage and then undergoes the formation of foregut invagination, the so-called 38 anterior intestinal portal (AIP), during early somitogenesis [10, 27, 28]. During AIP 39 formation and subsequent foregut tubulogenesis, a medial part of the foregut endoderm 40 sheet is roughly defined in the dorsal walls of the primitive gut tubes, and the lateral 41 foregut endoderm cells on both the left and right sides are relocated into the ventral 42 midline of the gut tube, leading to gut tube closure and embryonic turning. During 43 foregut closure, the liver, gallbladder and ventral pancreas primordia are separately 44 specified within the adjacent close regions of the ventral foregut endoderm, and the 45 formation of each primordium could be induced and maintained by distinct signaling 46 factors, such as FGFs, BMPs or TGFβ emitted from the cardiac mesoderm or transverse 47 septum [2, 16, 27]. 48 Sry-related HMG box gene-17 (Sox17) [7] is well known as a master regulatory gene 49 for initial endoderm specification [6, 15, 19, 22]. Sox17 is transiently activated in the 50 foregut endoderm during the early primitive stage (7.0 dpc) to early headfold stage (7.5 51 dpc) [6, 18, 25], and its expression is rapidly reduced by the late headfold stage. 52 Interestingly, Sox17 appeared to be reactivated in a small area …