eprintid: 31399
rev_number: 16
eprint_status: archive
userid: 6557
dir: disk0/00/03/13/99
datestamp: 2022-03-18 08:46:54
lastmod: 2022-03-29 06:00:02
status_changed: 2022-03-18 08:46:54
type: doctoralThesis
metadata_visibility: show
creators_name: Tomita, Takehito
title: The Origin and Regulation of Segmentation Clock Oscillation Dynamics in the Mouse Embryo
subjects: ddc-500
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
abstract: How cells coordinate their dynamic gene expression to produce patterns that transcend to the tissue scale is a fundamental question in biology. In the context of somitogenesis, the timing of segmentation is controlled by a molecular oscillator, the segmentation clock. The segmentation clock oscillations, particularly those regulated by Notch signaling, exhibit traveling wave patterns in the presomitic mesoderm (PSM) due to phase shifted oscillations along the AP axis. How their spatiotemporal dynamics are coordinated to produce such patterns is not fully understood. 
I first describe the origin of the traveling waves, with data obtained by imaging the onset of segmentation clock dynamics, at the gastrulating stages of the mouse embryo. Detailed analysis of the oscillations revealed that they are initially synchronous across space at its onset, but accumulate spatial phase shift over the first 6+ cycles, thereby leading to the emergence of traveling wave patterns. Such an accumulation of spatial phase shift agrees with the presence of a period gradient, where period mismatches between adjacent tissue increase the lag in oscillation phase over time. 
The existence of an oscillation period gradient has been reported in the later stages of the embryo across species, but not much is known about its regulation. FGF and Wnt signaling gradients present in the PSM have been nominated to control oscillation dynamics. However, past studies have reported that FGF signaling does not affect the segmentation clock, as segmentation pace was unaltered when FGF signaling was perturbed. Using an in vitro model of the PSM also showing an emergence of traveling waves, I characterized the effect of exogenous FGF signal on the wave dynamics in detail. The series of spatially and temporally designed FGF addition experiments indicate that FGF signaling governs the rate of change in oscillation period, or biologically, the rate of cellular maturation towards differentiation. Taken together, I uncover a novel role of FGF signaling in regulating spatiotemporal dynamics of segmentation clock oscillations in the mouse presomitic mesoderm.
date: 2022
id_scheme: DOI
id_number: 10.11588/heidok.00031399
ppn_swb: 1796034673
own_urn: urn:nbn:de:bsz:16-heidok-313999
date_accepted: 2022-02-04
advisor: HASH(0x55fc36c1a260)
language: eng
bibsort: TOMITATAKETHEORIGINA2022
full_text_status: public
place_of_pub: Heidelberg
citation:   Tomita, Takehito  (2022) The Origin and Regulation of Segmentation Clock Oscillation Dynamics in the Mouse Embryo.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/31399/1/Thesis_TT_2021.pdf