MRC National Institute for Medical Research, London
Science for Health
Elke Ober group project:
Liver progenitor specification
The digestive system, consisting of the alimentary canal and its accessory organs – including the liver, pancreas and gall bladder – is essential for maintaining body homeostasis. Within this system, the liver performs pivotal exocrine and endocrine functions, and has a unique ability to regenerate.
Endodermal-derived organs at 2 and 3 days of development
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The digestive organs form in close proximity to each other and are established by 3 dpf. Ventral views depicting tissue-specific stainings in conjunction with specific transgenic lines; liver(L), pancreas (P), intestinal bulb (IB), gall bladder (GB).
Liver precursors are specified at a precise anteroposterior position of the digestive tract by extrinsic signals from the adjacent lateral plate mesoderm. These progenitors form in close proximity to the prospective ventral pancreas and swim bladder, the structural homolog of the mammalian lung, within the foregut endoderm. This raises the question as to how these cells adopt fundamentally different identities. The mechanisms that direct foregut endoderm to a particular organ fate rely on the interplay of tissue competence and inductive signals. Therefore, liver fate specification requires not only tight regulation of these signals in time and space, but also correct integration at a cellular level. When this fine balance is perturbed, allocation of multipotent progenitors to a particular organ fate such as the liver or pancreas is defective, leading to improper expansion of one fate at the expense of another. Despite the important physiological functions of the liver, there are significant gaps in our understanding of the molecular mechanisms that define the competence of endoderm and restrict the inductive signals during early liver development.
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prometheus mutants exhibit a severe reduction of the liver. View of the developing liver and pancreas, both marked by the expression of Prox1 (red) and the extrahepatopancreastic ducts (blue).
We analyse liver organogenesis in wild type embryos and compare them to mutants, which display defects in liver development. These mutants were identified in a forward genetic screen and their analyses have uncovered roles for genes with very diverse biological functions in liver organogenesis, such as the chromatin remodelling factor Histone deacetylase1 and the mesodermally expressed signalling molecule Wnt2bb. Ongoing work aims to place these factors in the existing genetic network underlying liver development in vertebrates. Of great interest is how input from major signalling pathways, such as Wnt, Bmp and Fgf, is integrated temporally and spatially during liver specification.
Ober group
Recent publications
Research projects
- Liver progenitor specification
- Liver bud formation - regulation of shape and size
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