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Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis
Journal article   Open access   Peer reviewed

Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis

Sandeep Mukhi, Jinzhe Mao and Donald D. Brown
Proceedings of the National Academy of Sciences - PNAS, Vol.105(26), pp.8962-8967
06/23/2008
DOI: 10.1073/pnas.0803569105
PMCID: PMC2449347
PMID: 18574144
url
https://doi.org/10.1073/pnas.0803569105View
Published (Version of record) Open Access

Abstract

At metamorphosis the Xenopus laevis tadpole exocrine pancreas remodels in two stages. At the climax of metamorphosis thyroid hormone (TH) induces dedifferentiation of the entire exocrine pancreas to a progenitor state. The organ shrinks to 20% of its size, and ≈40% of its cells die. The acinar cells lose their zymogen granules and ≈75% of their RNA. The mRNAs that encode exocrine-specific proteins (including the transcription factor Ptf1a) undergo almost complete extinction at climax, whereas PDX-1 , Notch-1 , and Hes-1 , genes implicated in differentiation of the progenitor cells, are activated. At the end of spontaneous metamorphosis when the endogenous TH has reached a low level, the pancreas begins to redifferentiate. Exogenous TH induces the dedifferentiation phase but not the redifferentation phase. The tadpole pancreas lacks the mature ductal system that is found in adult vertebrate pancreases, including the frog. Exocrine pancreases of transgenic tadpoles expressing a dominant negative form of the TH receptor controlled by the elastase promoter are resistant to TH. They do not shrink when subjected to TH. Their acinar cells do not dedifferentiate at climax, nor do they down-regulate exocrine-specific genes or activate Notch-1 and Hes-1 . Even 2 months after metamorphosis these frogs have not developed a mature ductal system and the acinar cells are abnormally arranged. The TH-dependent dedifferentiation of the tadpole acinar cells at climax is a necessary step in the formation of a mature frog pancreas.
Biological Sciences dedifferentiation gene expression thyroid hormone Thyroid hormone receptor dominant negative

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