title: Cellular mechanisms underlying tissue pattern emergence in the developing embryo
creator: Moghe, Prachiti
subject: 500
subject: 500 Natural sciences and mathematics
subject: 570
subject: 570 Life sciences
description: 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
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/33393/1/Thesis_20230320_PrachitiMoghe.pdf
identifier: DOI:10.11588/heidok.00033393
identifier: urn:nbn:de:bsz:16-heidok-333933
identifier:   Moghe, Prachiti  (2024) Cellular mechanisms underlying tissue pattern emergence in the developing embryo.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/33393/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng