TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/37071/
CY  - Heidelberg
AV  - restricted
N2  - Patterns are ubiquitous in the natural world and fundamental to life. Embryonic development ? the process by which organisms take shape ? is itself an act of patterning, requiring the precise spatiotemporal coordination of multiple co-occurring processes. This coordination relies on mechanisms that can store, transmit, and interpret high-content biological information underlying these developmental programs. How such information is encoded and decoded to give rise to patterning events is one of the central questions in developmental biology.
Somitogenesis, the establishment of segmental patterning along the main body axis of vertebrate embryos, is one of the most studied examples of biological pattern formation. It involves the sequential subdivision of the vertebrate embryonic axis into repeated units of tissue called somites, the precursors of vertebrae and their associated structures. This process is regulated by the segmentation clock, a network of genetic oscillators active in the presomitic mesoderm (PSM). These periodic oscillations are cell-autonomous yet locally synchronized and spatiotemporally organised to give the impression of a spatiotemporal wave pattern, that periodically travels from the posterior to the anterior end of the PSM. Each cycle, a new somite forms at the site of wave arrest at the anterior PSM.
While there is broad consensus that the segmentation clock regulates the timing of somite formation, understanding of how positional information for the placement of somite boundaries is specified during this process remains limited. Two main theoretical models have been proposed to explain the spatiotemporal regulation of somitogenesis: the clock and wavefront model and the phase-shift model. According to the clock and wavefront model, temporal information encoded in the segmentation clock interacts with an independent positional reference (the wavefront) to determine the site of somite boundary formation. Within the framework of the phase-shift model, both temporal and spatial information for somite patterning is encoded in the oscillatory dynamics, particularly in their spatial phase profile. These models make clear, distinct predictions about somite patterning and, specifically, the phenotypic consequences of altering the segmentation clock period. However, technical limitations have so far prevented direct experimental testing of these models.
Recently, a microfluidic system was developed for the experimental manipulation of the segmentation clock in mouse PSM spreadouts, a two-dimensional assay of the presomitic mesoderm. This approach enabled the synchronization of the segmentation clock to periodically supplied pulses of signalling modulators: a process known as entrainment. In this thesis, I optimised a similar microfluidics-based entrainment system for the culture of intact, three-dimensional presomitic mesoderm tissue from mouse embryonic tails, establishing a more physiologically relevant system for the study of somitogenesis. I then used this experimental platform to entrain the segmentation clock, slowing down its period as well as the timing of somite formation, and monitored the resulting tissue-level responses to these controlled perturbations.
I observed the appearance of transient morphological phenotypes in the forming somites of entrained samples. The characterization of these phenotypes, together with their timing relative to the transition of the tissue into an entrained state, provided new insights into the mechanisms regulating the spatiotemporal coordination of somitogenesis in the mouse PSM. Taken together, my findings challenge the classical clock and wavefront model of somitogenesis and, instead, provide evidence in support of a functional role for the phase wave pattern in the transmission of spatiotemporal cues for somite patterning, as proposed by the phase-shift model.
Y1  - 2026///
A1  - Gioè, Simona
ID  - heidok37071
TI  - Investigating the functional role of oscillatory signalling via experimental entrainment of the somite segmentation clock
ER  -