Depletion of definitive gut endoderm inSox17-null mutant mice

Abstract

In the mouse, the definitive endoderm is derived from the epiblast during gastrulation, and, at the early organogenesis stage, forms the primitive gut tube, which gives rise to the digestive tract, liver, pancreas and associated visceral organs. The transcription factors, Sox17 (a Sry-related HMG box factor) and its upstream factors, Mixer (homeobox factor) and Casanova (a novel Sox factor), have been shown to function as endoderm determinants in Xenopus and zebrafish, respectively. However, whether the mammalian orthologues of these genes are also involved with endoderm formation is not known. We show that Sox17–/– mutant embryos are deficient of gut endoderm. The earliest recognisable defect is the reduced occupancy by the definitive endoderm in the posterior and lateral region of the prospective mid- and hindgut of the headfold-stage embryo. The prospective foregut develops properly until the late neural plate stage. Thereafter, elevated levels of apoptosis lead to a reduction in the population of the definitive endoderm in the foregut. In addition, the mid- and hindgut tissues fail to expand. These are accompanied by the replacement of the definitive endoderm in the lateral region of the entire length of the embryonic gut by cells that resemble the visceral endoderm. In the chimeras, although Sox17-null ES cells can contribute unrestrictedly to ectodermal and mesodermal tissues, few of them could colonise the foregut endoderm and they are completely excluded from the mid- and hindgut endoderm. Our findings indicate an important role of Sox17 in endoderm development in the mouse, highlighting the idea that the molecular mechanism for endoderm formation is likely to be conserved among vertebrates.

Sequential enhancer state remodelling defines human germline competence and specification

“…Since the human and mouse PRDM1 loci show conservation of four out of five SOX motifs in their enhancers and promoters ( Extended Data Fig. 8f ), SOX17 can likely regulate mouse PRDM1 as exemplified by their co-expression in mouse visceral endoderm 12 , 73 , 74 . Altogether, SOX17 is the critical regulator of hPGC fate, while PRDM1, PRDM14, and potentially SOX2 fulfil this role in mice 8 , 17 , 75 .…”

Development of Functional Thyroid C Cell-like Cells from Human Pluripotent Cells in 2D and in 3D Scaffolds

“…The induced cells were analysed at day 6 for the expression of vertebrate DE markers [ 42 , 43 ] FOXA2, CER1, CDH2 (N-cadherin), and SOX17 by qPCR, and we observed an upregulation of these genes together with a downregulation of the pluripotency marker, OCT4 , while CDH1 (E-cadherin) was unchanged ( Figure 2 c). A robust increase in a gene expressed in the anterior foregut endoderm (AFE), NKX2.1 (also known as thyroid transcription factor 1, TTF1 ) [ 26 ], and FOXA1 [ 34 ], was also found.…”

Adaptation of a Commonly Used, Chemically Defined Medium for Human Embryonic Stem Cells to Stable Isotope Labeling with Amino Acids in Cell Culture

“…SOX17 belongs to the SOX family of DNA-binding transcription factors . It is known to be a key factor in various developmental processes involving the formation of definitive endoderm and mesoderm . It is thus expected that SOX17 is overexpressed in HeLa as compared to pluripotent cell systems.…”