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      Orchestrating liver development

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          Abstract

          The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis.

          Abstract

          Summary: This review summarises the complex interplay between cellular lineages, signalling pathways, and transcriptional programs necessary to form a vertebrate liver.

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          Most cited references164

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          Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4.

          The transcription factors HNF3 (FoxA) and GATA-4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in embryos. To understand how they access sites in silent chromatin, we assembled nucleosome arrays containing albumin enhancer sequences and compacted them with linker histone. HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes. The ability of HNF3 to open chromatin is mediated by a high affinity DNA binding site and by the C-terminal domain of the protein, which binds histones H3 and H4. Thus, factors that potentiate transcription in development are inherently capable of initiating chromatin opening events.
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            Organogenesis and development of the liver.

            Embryonic development of the liver has been studied intensely, yielding insights that impact diverse areas of developmental and cell biology. Understanding the fundamental mechanisms that control hepatogenesis has also laid the basis for the rational differentiation of stem cells into cells that display many hepatic functions. Here, we review the basic molecular mechanisms that control the formation of the liver as an organ. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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              Vertebrate endoderm development and organ formation.

              The endoderm germ layer contributes to the respiratory and gastrointestinal tracts and to all of their associated organs. Over the past decade, studies in vertebrate model organisms, including frog, fish, chick, and mouse, have greatly enhanced our understanding of the molecular basis of endoderm organ development. We review this progress with a focus on early stages of endoderm organogenesis including endoderm formation, gut tube morphogenesis and patterning, and organ specification. Lastly, we discuss how developmental mechanisms that regulate endoderm organogenesis are used to direct differentiation of embryonic stem cells into specific adult cell types, which function to alleviate disease symptoms in animal models.
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                Author and article information

                Journal
                Development
                Development
                DEV
                develop
                Development (Cambridge, England)
                The Company of Biologists
                0950-1991
                1477-9129
                15 June 2015
                15 June 2016
                : 142
                : 12
                : 2094-2108
                Affiliations
                [1 ]Department of Surgery, Weill Cornell Medical College , New York, NY 10065, USA
                [2 ]Department of Developmental and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029, USA
                Author notes
                [* ]Author for correspondence ( valerie.gouon-evans@ 123456mssm.edu )
                Article
                DEV114215
                10.1242/dev.114215
                4483763
                26081571
                843269ec-e974-497f-aa68-9d8da3d0ed60
                © 2015. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                Categories
                Review

                Developmental biology
                cholangiocyte,hepatoblast,hepatocyte,liver development,transcription factors
                Developmental biology
                cholangiocyte, hepatoblast, hepatocyte, liver development, transcription factors

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