dc.contributor.author
Willnow, David
dc.date.accessioned
2019-05-13T08:33:34Z
dc.date.available
2019-05-13T08:33:34Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/24566
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-2329
dc.description.abstract
Liver and pancreas are derivatives of the endodermal germ layer that become specified
around E8.5 in the mouse embryo. The pancreas arises from two distinct regions in the
foregut, one dorsally, one ventrally located. Interestingly, the ventral pancreatic domain
overlaps with the prospective hepatic endoderm and both organ rudiments develop in close
proximity to one another throughout early development. Previous analyses suggested that
liver and ventral pancreas arise from a common progenitor domain. However, this hypothesis
had not been validated in mammalian embryos in vivo. In addition, the cellular and tissue
dynamics defining hepatic and pancreatic lineage segregation from this presumed common
progenitor domain remained elusive.
In this study, I applied complementary genetic lineage tracing approaches in mouse models
to label early hepato-pancreatic progenitors and to follow their contribution to liver and
pancreas in vivo. By employing a combination of unicolor and multicolor (Confetti) reporter
systems, I traced the common origin of liver and ventral pancreas to a bipotent progenitor
domain situated in the ventral foregut. In addition, I uncovered the surprising fact that ventral
pancreatic cells retain the bipotent nature of these ventral foregut progenitors and contribute
to the growing liver rudiment throughout early organogenesis. In vivo analyses of marker
gene expression suggested that this progenitor population is characterized by the concurrent
expression of the transcription factors Prox1, Pdx1, and Sox17. I substantiated these findings
of pancreatic cell fate plasticity by detailed in vivo time course analyses of cell numbers and
proliferation dynamics in the hepato-pancreatic organ system. Finally, I identified Robo-Slit
signaling as an essential signaling pathway to maintain pancreatic identity and to prevent
aberrant hepatic fate acquisition within the ventral pancreatic domain.
Taken together, by combining genetic lineage tracing and quantitative immunohistochemical
analyses in genetic mouse models in vivo, I uncovered that ventral pancreatic cells display a
hitherto unappreciated level of cell fate plasticity fundamental for proper development of
ventral foregut derivatives.
en
dc.format.extent
XIV, 152 Seiten
dc.rights.uri
http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen
dc.subject
Organogenesis
en
dc.subject.ddc
500 Natural sciences and mathematics::570 Life sciences::570 Life sciences
dc.title
Elucidating hepatic and pancreatic fate acquisition during early mouse development
dc.contributor.gender
male
dc.contributor.firstReferee
Spagnoli, Francesca M.
dc.contributor.furtherReferee
Köhrle, Josef
dc.date.accepted
2019-05-02
dc.identifier.urn
urn:nbn:de:kobv:188-refubium-24566-3
dc.title.translated
Eluzidierung der Zellschicksalsentscheidung hepatischer und pankreatischer Zellen während der frühen Embryonalentwicklung in der Maus
de
refubium.affiliation
Biologie, Chemie, Pharmazie
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free
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open access
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