Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues
Open accessAbstract
The location and movement of mammalian gut tissue progenitors, prior to the expression of tissue-specific genes, has been unknown, but this knowledge is essential to identify transitions that lead to cell type specification. To address this, we used vital dyes to label exposed anterior endoderm cells of early somite stage mouse embryos, cultured the embryos into the tissue bud phase of development, and determined the tissue fate of the dye labeled cells. This approach was performed at three embryonic stages that are prior to, or coincident with, foregut tissue patterning (1-3 somites, 4-6 somites, and 7-10 somites). Short-term labeling experiments tracked the movement of tissue progenitor cells during foregut closure. Surprisingly, we found that two distinct types of endoderm-progenitor cells, lateral and medial, arising from three spatially separated embryonic domains, converge to generate the epithelial cells of the liver bud. Whereas the lateral endoderm-progenitors give rise to descendants that are constrained in tissue fate and position along the anterior-posterior axis of the gut, the medial gut endoderm-progenitors give rise to descendants that stream along the anterior-posterior axis at the ventral midline and contribute to multiple gut tissues. The fate map reveals extensive morphogenetic movement of progenitors prior to tissue specification, it permits a detailed analysis of endoderm tissue patterning, and it illustrates that diverse progenitor domains can give rise to individual tissue cell types.
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Signals from the overlying cardiac mesoderm and septum transversum mesenchyme (STM) induce hepatoblast transition into a pseudostratified columnar epithelium and their invasion of the STM by E9.5.
“Signals from the overlying cardiac mesoderm and septum transversum mesenchyme (STM) induce their transition into a pseudostratified columnar epithelium and their invasion of the STM by E9.5”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tremblay and Zaret, 2005
The section ‘Liver progenitors within the ventral midline of the endoderm lip’ reports liver-bud descendants invading mesenchyme, and the Fig. 2 caption likewise describes liver-bud cells invading local mesenchyme. Our copy does not establish that cardiac mesoderm and STM signals induce this invasion or a transition to pseudostratified columnar epithelium by E9.5. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHepatoblasts, the bipotent progenitor for hepatocytes and cholangiocytes, develop from the definitive endoderm by embryonic day E8.75.
“Hepatoblasts, the bipotent progenitor for hepatocytes and cholangiocytes, develop from the definitive endoderm by embryonic day (E)8.75”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tremblay and Zaret, 2005
The section ‘Identifying progenitors for the liver and other ventral tissues in the lateral endoderm’ (page not provided) traces mouse endoderm cells to the liver bud and reports liver progenitors at the 7–10-somite stage. The Fig. 2 caption identifies HNF4α as a hepatoblast marker. Our copy does not establish the specific E8.75 timing or state that these hepatoblasts are bipotent progenitors of hepatocytes and cholangiocytes. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe embryonic liver is formed from the posterior ventral foregut endoderm, which invades the STM in response to migratory cues.
“The embryonic liver is formed from the posterior ventral foregut endoderm, which invades the STM in response to migratory cues”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tremblay and Zaret, 2005
The fate-mapping results and Fig. 2 caption show that ventral endoderm progenitors contribute to the mouse liver bud and that labeled liver-bud cells invade local mesenchyme. But the paper describes two distinct progenitor populations, not a solely posterior ventral-foregut origin, and the passages do not identify the mesenchyme as STM or establish migratory cues as the cause of invasion. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe temporal emergence of hepatoblasts is in line with previous studies, with specification from the endoderm in early organogenesis (E8.75), migration at E9.5, and the beginnings of hepatoblast function at E10.5.
“The temporal emergence of hepatoblasts is in line with previous studies, with specification from the endoderm in early organogenesis (E8.75), migration at E9.5, and the beginnings of hepatoblast function at E10.5”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tremblay and Zaret, 2005
The Discussion (page not available in our copy) traces liver progenitors from early endoderm, describes their movement, and shows labeled descendants invading the mesenchyme of the liver bud. It does not establish specification at E8.75, migration specifically at E9.5, or the onset of hepatoblast function at E10.5. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThese domains converge to generate the epithelial cells of the liver bud.
“These domains converge to generate the epithelial cells of the liver bud [13].”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [13]
Pancreatic progenitors were rarely labeled by this lineage tracing, suggesting that Pyy may not mark the identical domain.
“However, pancreatic progenitors were rarely labeled by this lineage tracing [13] suggesting that Pyy may not mark the identical domain.”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [13]
Tremblay et al. identified two distinct types of definitive endoderm progenitor cells, lateral and medial, arising from three spatially separated embryonic domains.
“They identified two distinct types of DE progenitor cells, lateral and medial, arising from three spatially separated embryonic domains.”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [13]
FGF and BMP signaling have previously been shown to coordinate the specification of anterior and posterior hepatic endodermal populations, respectively.
“while FGF and BMP signaling have previously been shown to coordinate the specification of anterior and posterior hepatic endodermal populations, respectively”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tremblay and Zaret, 2005
The Discussion describes fate mapping of liver progenitors before hepatic specification, and the movement section tracks their positions during foregut closure. Searches for FGF, BMP, and bone morphogenetic protein found no passage in our copy assigning FGF to anterior and BMP to posterior hepatic endoderm specification. (LLM, conf=0.74)
Experimental — accuracy not yet measuredFGF4, expressed in the neighboring cardiac mesoderm, can induce differentiation of ventral foregut endoderm in a concentration-dependent manner.
“FGF4, which is expressed in the neighboring cardiac mesoderm, can induce the differentiation of ventral foregut endoderm in a concentration-dependent manner [13,14].”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [13]
The Discussion mentions inductive signaling between mesoderm and endoderm but does not identify FGF4 or describe a concentration-dependent effect. Searches for FGF4 and cardiac-mesoderm FGF signaling found only a References entry for a study of FGF thresholds, not a passage in this paper addressing the attributed claim. No page number is available in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measured
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Cites
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Self-citation
- Authors
- Tremblay, K. D., & Zaret, K. S.
- Affiliations
- Fox Chase Cancer Center (US)
- Corresponding author
- Zaret, Kenneth S.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 280
- Issue
- 1
- Pages
- 87-99
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W1970621119
- Cited by
- 299
- References
- 4
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 16 · 2019: 21 · 2018: 15 · 2017: 18 · 2016: 13 · 2015: 15 · 2014: 17 · 2013: 19 · 2012: 20
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- ScholarWorks@UMassAmherst (University of Massachusetts Amherst) (submittedVersion)
- Funders
- G. Harold and Leila Y. Mathers Foundation
- National Institutes of Health (GM36477)
- Fox Chase Cancer Center
- National Cancer Institute
- National Institute of General Medical Sciences (R01GM036477, GM 36477, R01-GM36477)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK064063)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- anterior endoderm, fate mapping, cell migration, anterior-posterior axis, somite stage, mouse embryo
- MeSH terms
- Animals, Cell Movement, Digestive System, Embryo, Mammalian, Embryonic Structures, Endoderm, Liver, Mice, Inbred C3H, Morphogenesis, Stem Cells, Cell Lineage, Body Patterning, Cell Proliferation, Mice
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