Das Herz ist das erste Organ, das sich während der Embryonalentwicklung bildet und durch die Verteilung von Nährstoffen und Sauerstoff für die Lebenserhaltung von Geweben und Organen verantwortlich ist. Die Herzentwicklung benötigt die koordinierte Rekrutierung von zwei Herzvorläufer-Populationen, dem ersten und zweiten Herzfeld, welche sich aus einer gemeinsamen Vorläuferzellpopulation während der Gastrulation bilden. In der vorliegenden Arbeit wurde der Einfluss der Bmp- und Wnt-Signalwege auf die frühe Herzentwicklung in Mäusen untersucht. Dafür wurden mit Hilfe der Cre/LoxP-Technik inaktivierende und aktivierende Mutationen im Bmp-Rezeptor Ia (BmpRIa) und im zentralen Modulator des Wnt-Signalweges, beta-Catenin, in Zellen des Mesoderms eingeführt, aus dem beide Herzfelder hervorgehen. Inaktivierende Mutationen im BmpRIa führen zum Verlust von erster Herzfeldderivate und zum Expressionsverlust von Genen, welche für die Aufrechterhaltung und Spezialisierung des ersten Herzfeldes in den späteren linken Ventrikel wichtig sind. In Mäusen mit inaktivierenden Mutationen in beta-Catenin bildet sich das erste Herzfeld korrekt, während die Entwicklung des zweiten Herzfeldes, z.B. die rechtsgerichtete Windung des linearen Herzrohres sowie Bildung des Ausflusstrakts und rechten Ventrikels, gestört ist. Die Genexpression von Bmp4 und Islet1 in Vorläufern des zweiten Herzfeldes ist stark reduziert, während aktivierende Mutationen in beta-Catenin diese verstärken und die Bildung des linearen Herzrohres stören. Diese Ergebnisse zeigen, dass beta-Catenin für die Entwicklung des zweiten Herzfeldes entscheidend ist, und dass die Aktivierung des Wnt/beta-Catenin-Signalweges zeitlich und räumlich präzise reguliert werden muss, damit sich ein windendes lineares Herzrohr entwickeln kann. Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass die BmpRIa- und Wnt/beta-Catenin-Signalwege unterschiedliche Rollen während der Musterbildung in der frühen Herzentwicklung spielen. / The vertebrate heart is the first organ that forms during embryonic development. Heart formation requires the coordinated recruitment of multiple cardiac progenitor cell populations derived from both the first and second heart fields, which arise from a common progenitor at gastrulation. In this study we have ablated the Bmp receptor 1a (BmpRIa) and the Wnt effector beta-Catenin in the developing heart of mice using MesP1-cre, which acts in early mesoderm progenitors that contribute to both first and second heart fields. Remarkably, the entire cardiac crescent and later the primitive ventricle were absent in MesP1-cre; BmpR1a loss-of-function mutants. While myocardial progenitor and differentiation markers were detected in the small, remaining cardiac field in these mutants, first heart field markers, which are required for the maintenance and specification of first heart field derivatives, were not expressed. We conclude from these results that Bmp receptor signaling is crucial for the specification of the first heart field. In MesP1-cre; beta-Catenin loss-of-function mutants, cardiac crescent formation as well as first heart field markers were not affected, although cardiac looping and right ventricle formation were blocked. Expression of Isl1 and Bmp4 in second heart field progenitors was strongly reduced. In contrast, in gain-of-function mutation of beta-Catenin using MesP1-cre we revealed an expansion of Isl1 and Bmp4 expressing cells, although the heart tube was not formed. We conclude from these results that Wnt/beta-Catenin signaling regulates second heart field development, and that a precise amount and/or timing of Wnt/beta-Catenin signaling is required for proper heart tube formation and cardiac looping. In conclusion, we have shown that Bmp and canonical Wnt signaling have distinct roles during early cardiogenesis in mice.

This study deals with modern mission history in north eastern Africa. When the rigid Islamistic Mahdi regime in the Sudan was defeated by an Anglo-Egyptian army in 1898, H G Guinness and K Kumm came to Aswan and initiated the Sudan Pionier Mission (SPM) in 1900. The SPM had its spiritual roots in the Holiness Movement and became an interdenominational German-based faith mission. Although the SPM was started in Aswan to advance from there to the south to evangelize animistic people groups in the Eastern Sudan, the SPM actually consolidated its work in and around Aswan for internal and external reasons. Thus, the focus of the SPM shifted from an animistic to an Islamic audience with a special emphasis on the Nile-Nubians occupying the Nile valley between Aswan and Dongola. This study contributes generally to the historiography of the SPM between 1990 until 1966 and analyzes especially the development of the SPM into a mission among the Nile-Nubians during this period. The ethnic groups of the Nile-Nubians will be introduced and their historical, political, social, economic, linguistic and religious situation will be presented. This thesis further describes the topographical development of the SPM and its missiological approach. A special emphasis is given to the life story of the Kunuuzi Nubian convert Samu’iil Ali Hiseen (SAH-1863-1900) and his multifaceted contribution to the work of the SPM. SAH was the first Nubian evangelist in modern times and the major stakeholder of the Nubian vision. Neither the history of the SPM as “Nubian Mission” nor the life and work of SAH have been researched and presented before. / Christian Spirituality, Church History and Missiology / D. Th. (Missiology)

This study deals with modern mission history in north eastern Africa. When the rigid Islamistic Mahdi regime in the Sudan was defeated by an Anglo-Egyptian army in 1898, H G Guinness and K Kumm came to Aswan and initiated the Sudan Pionier Mission (SPM) in 1900. The SPM had its spiritual roots in the Holiness Movement and became an interdenominational German-based faith mission. Although the SPM was started in Aswan to advance from there to the south to evangelize animistic people groups in the Eastern Sudan, the SPM actually consolidated its work in and around Aswan for internal and external reasons. Thus, the focus of the SPM shifted from an animistic to an Islamic audience with a special emphasis on the Nile-Nubians occupying the Nile valley between Aswan and Dongola. This study contributes generally to the historiography of the SPM between 1990 until 1966 and analyzes especially the development of the SPM into a mission among the Nile-Nubians during this period. The ethnic groups of the Nile-Nubians will be introduced and their historical, political, social, economic, linguistic and religious situation will be presented. This thesis further describes the topographical development of the SPM and its missiological approach. A special emphasis is given to the life story of the Kunuuzi Nubian convert Samu’iil Ali Hiseen (SAH-1863-1900) and his multifaceted contribution to the work of the SPM. SAH was the first Nubian evangelist in modern times and the major stakeholder of the Nubian vision. Neither the history of the SPM as “Nubian Mission” nor the life and work of SAH have been researched and presented before. / Christian Spirituality, Church History and Missiology / D. Th. (Missiology)