Functional analysis of the cardiogenic transcription factor mespa in mesoderm differentiation in Xenopus laevis

Roeßler, Christian (2021): Functional analysis of the cardiogenic transcription factor mespa in mesoderm differentiation in Xenopus laevis. Dissertation, LMU München: Medizinische Fakultät

Abstract

Progenitors of the heart, the vasculature, musculature, connective and supporting tissue, the gonads, the kidneys and lower urinary tract derive from the mesodermal germ layer. The knowledge about the highly complex processes and involved factors during induction and differentiation of progenitor cells are of great scientific and medical interest. It helps understand the underlying molecular genetical basics of congenital malformations on one hand and develop new therapeutic options for personalised medicine on the other hand. The bHLH transcription factor mesp1 became the focus of research as master regulator of cardiogenesis. It was shown that mesp1 is already expressed early during gastrulation and that mesp1 activates additional important regulators of cardiovascular differentiation. The knockout of the mesp1 gene in mice leads to a so-called cardia bifida, a failed fusion of the heart tube, whereas the simultaneous deactivation of mesp1 and the related mesp2 result in a complete loss of the heart anlagen. Since mesp1 and its homologue mespa of the African claw frog Xenopus laevis are activated early, further exceeding functions concerning the differentiation of further mesodermal tissues are supposed. Xenopus laevis is a particularly proper model organism due to its easy manipulability and approachability of all developmental stages. In this study, relations between mespa and mesodermal precursor cells have been examined in different developmental stages based on gene expression analysis after knockout or overexpression of mespa. It was shown, that mespa is required for the expression of early mesodermal markers eomes and xbra during gastrulation and neurulation. Moreover, mespa plays a role in skeletomyogenesis and in the development of facial structures, but is not sufficient to activate myogenic markers on its own. Furthermore, it was demonstrated that mespa is involved in the development of precursors of vasculogenesis and embryonic haematopoiesis. Formerly described effects on the epithelial-to-mesenchymal transition could not be confirmed. Likewise, no direct relation towards nephrogenesis was shown. In conclusion, it was demonstrated that mespa exerts extensive functions during the development of mesodermal tissues.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: mespa, Xenopus laevis, cardiogenesis, mesoderm differentiation
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 18. Februar 2021
• 1. Bericht­erstatter:in: Rupp, Ralph