eprintid: 33393
rev_number: 19
eprint_status: archive
userid: 7455
dir: disk0/00/03/33/93
datestamp: 2023-06-21 13:22:25
lastmod: 2024-06-21 07:50:56
status_changed: 2023-07-25 07:14:14
type: doctoralThesis
metadata_visibility: show
creators_name: Moghe, Prachiti
title: Cellular mechanisms underlying tissue pattern emergence in the developing embryo
subjects: ddc-500
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
abstract: Mammalian embryo development is highly regulative in nature, with cell fate being
reversible to compensate for changes in the nascent environment during early stages.
In such regulative paradigms, the complex interactions between cellular processes
to accomplish precision in patterning of tissues present exciting open questions in
biology. In this thesis, I explore the patterning mechanisms underlying blastocyst
maturation during pre-implantation development of the mouse embryo. Development
of the mammalian blastocyst involves the progressive segregation of the inner
cell mass comprising the embryonic epiblast and the extra-embryonic primitive endoderm,
and the expansion of a fluid-filled cavity. A gene regulatory network between
fibroblast growth factor signalling and cell fate-specific transcription factors establishes
the characteristic salt-and-pepper distribution of epiblast and primitive endoderm
cells in the early blastocyst. Following the establishment of the two precursor
populations, cells spatially segregate into distinct domains within the embryo. The
primitive endoderm forms an epithelial layer at the surface of the fluid cavity, with
the pluripotent epiblast enclosed between the trophectoderm and the primitive endoderm.
Symmetry-breaking in the blastocyst has been the focus of much research in
the past decades. However, a coherent mechanism of blastocyst pattern emergence
coordinating cell fate specification, sorting and morphogenesis is lacking. Using reduced
systems and advanced live-image analysis, I established a method to characterise
cell sorting during fate segregation. Further, combined with biophysical measurements
and perturbations, I investigate the interplay between cytoskeletal dynamics,
cell migration, and polarity in driving fate segregation. I demonstrate that cell sorting
in the inner cell mass is characterised by active migration of primitive endoderm cells
towards the cavity surface. The primitive endoderm cells in the early blastocyst display
autonomous acquisition of apical polarity, a defining feature essential for their
proper segregation into a single epithelial layer enveloping the epiblast. Moreover,
in contrast to epiblast cells, apical polarity in primitive endoderm cells facilitates the
lowering of surface tension upon encountering the cavity surface, thus being sufficient
for cell positioning. Lastly, I provide evidence that cell fate plasticity is lost in
late blastocysts due to which the fixed lineage composition of the inner cell mass is optimal exclusively for a particular embryo size. Altogether, the findings presented
in this work provide mechanistic insights into segregation of cell fates in the mammalian
blastocyst and put forth a novel understanding of robust patterning during
embryonic development.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00033393
ppn_swb: 1891981323
own_urn: urn:nbn:de:bsz:16-heidok-333933
date_accepted: 2023-06-19
advisor: HASH(0x559e37d08b28)
language: eng
bibsort: MOGHEPRACHCELLULARME
full_text_status: public
place_of_pub: Heidelberg
citation:   Moghe, Prachiti  (2024) Cellular mechanisms underlying tissue pattern emergence in the developing embryo.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/33393/1/Thesis_20230320_PrachitiMoghe.pdf