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Defining limitations to the regenerative ability of limb connective tissue cells in Xenopus laevis
Tzi-Yang Lin
Art der Arbeit
Dissertation
Universität
Universität Wien
Fakultät
Zentrum für Molekulare Biologie
Studiumsbezeichnung bzw. Universitätlehrgang (ULG)
Doctor of Philosophy-Doktoratsstudium NAWI Bereich Lebenswissenschaften (DissG: Molekulare Biologie)
Betreuer*in
Elly Tanaka
DOI
10.25365/thesis.72013
URN
urn:nbn:at:at-ubw:1-16785.64742.845714-7
Link zu u:search
(Print-Exemplar eventuell in Bibliothek verfügbar)
Abstracts
Abstract
(Deutsch)
The ability to regenerate a fully patterned limb exists in salamanders, while post-metamorphic frogs can only regenerate a hypomorphic spike, which is an unbranched, unsegmented cartilage covered with skin tissues. Upon limb amputation, both axolotls and the African clawed frogs form a blastema, which is composed of proliferative progenitor cells accumulating at the amputation plane. So far, the cellular and molecular mechanisms that are responsible for the differences between the blastema cells in both species are not completely understood. To address this question, we performed regeneration time courses of both axolotl and frogs where we systematically compared the molecular and cellular behaviours of the limb connective tissue (CT) cells, which is known to play key roles in axolotl limb regeneration. We first confirmed that, as in the case of axolotls, a frog blastema is mainly composed of the descendants of limb CT cells by generating and characterizing Prrx1:CreER transgenic frog lines which allowed the labelling and tracing of the limb CT cells. Single cell RNA-seq analysis over the regeneration time course and heterochronic transplantation assay into limb buds showed that axolotl CT cells dedifferentiated and were able to integrate into multiple lineages of the limb buds, including cartilages. On the other hand, frog CT cells only partially dedifferentiated and did not acquire the potency to integrate into the cartilage of the developing limb buds. The result of the transplantation assay indicated the existence of cell intrinsic limitations of frog CT cells. Further analysis on the single cell RNA-seq dataset revealed that the chondrogenic pathway of the spike cartilage was molecular distinct from the case during limb development. Overall, my work showed that dedifferentiation of the limb CT cells correlated with the regeneration capability of the organisms and strongly suggests that the cell intrinsic limitations are the key hinderance to complete regeneration.
Schlagwörter
Schlagwörter
(Deutsch)
limb regeneration connective tissue cells dedifferentiation Xenopus Axolotls lineage tracing single cell RNA-seq analysis
Autor*innen
Tzi-Yang Lin
Haupttitel (Englisch)
Defining limitations to the regenerative ability of limb connective tissue cells in Xenopus laevis
Publikationsjahr
2022
Umfangsangabe
110 Seiten : Illustrationen
Sprache
Englisch
Beurteiler*innen
Jonathan Slack ,
Ulrich Technau
Klassifikation
42 Biologie > 42.13 Molekularbiologie
AC Nummer
AC16597647
Utheses ID
63180
Studienkennzahl
UA | 794 | 685 | 490 |