Addressing the impact of surface ectoderm and somitic mesoderm development on neural tube morphogenesis.

Projektbeschreibung

Welche Kräfte hinter der Entwicklung des Nervensystems stecken

Im Lauf der Entwicklung entsteht das Nervensystem aus der Neuralplatte. Diese komplexe Struktur erfordert die Koordination mehrerer Gewebe. Die Neuralplatte wölbt sich und schließt sich im Endeffekt zu einem Neuralrohr, aus dem sich das Gehirn und das Rückenmark bilden. Geschieht das nicht, kommt es zu Neuralrohrdefekten. Das Interesse des EU-finanzierten Projekts Neural Tube gilt der Erforschung des Prozesses des Schließens des Neuralrohrs aus mechanischer Sicht. Ziel des Forschungsteams ist, unter Einsatz von Xenopus laevis und Mausembryonen als Modellsysteme den Beitrag anderer Gewebe zum Schließen des Neuralrohrs zu untersuchen. Die Projektergebnisse werden Grundwissen über den Ursprung der menschlichen Entwicklung und der Neuralrohrdefekte liefern.

Ziel

Neural tube closure (NTC) is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective NTC leads to neural tube defects (NTDs), which are one of the most common human birth defects. During NTC Convergent Extension (CE) leads to the narrowing and elongation of the neural plate (NP) and Apical Constriction (AC) drives the bending of the tissue. While the role of the aforementioned morphogenetic events for NTC has been studied extensively how the development of tissues mechanically coupled with the NP affects NTC remains poorly understood. Here, we aim to elucidate the influence of surface ectoderm (SE) and somitic mesoderm (SM) morphogenesis on NTC. To achieve our goals, we will employ an interdisciplinary research plan using Xenopus laevis and mouse embryos as model systems. First, to understand the contribution of SE and SM morphogenesis on NTC (AC and CE) we will specifically inhibit these processes using morpholino mediated protein knock-down in Xenopus embryos and tissue-specific knock-out and knock-in models in mice embryos. Subsequently, we will directly assess the impact of SE and SM tissue tension on NTC by modulating tissue tension in Xenopus embryos through optogenetic tools and mutant constructs in conjunction with live imaging. We will go on to examine how SE and SM influence the mechanical landscape of the NP using force inference techniques in Xenopus and mouse embryos in conjunction with loss of function approaches described above. Finally, we will examine how mechanical coupling between the NP with both the SE and SM affects the mechanosensitive elements responsible for CE and AC. Overall the data produced by the proposed work will uncover the role of SE and SM morphogenesis on NTC expanding our understanding of human NTDs, while at the same time providing precious insights with respect to the coordination and coupling of mechanical force generators during embryonic development.