Mechanisms and dynamics of size regulation and lumen formation in mouse double embryos

Mouse embryogenesis is a paradigmatic example of regulative development, as embryos are able to compensate for alterations in the number of cells and to generate normal-sized pups. It was previously showed that double-sized embryos achieve downsizing after implantation but before gastrulation ensues. However, the exact timing and cellular mechanisms that regulate the morphogenetic events during double embryos development are still elusive. Here, we present a detailed morphological staging of post-implantation double-embryos, which reveals that size regulation occurs between E5.25 and E5.5, thus earlier than previously anticipated. At the same time, the embryonic tissue undergoes a process of epithelialization to form a lumen that later will become the pro-amniotic cavity, an essential morphogenetic event that is delayed in double embryos compared to normal-sized embryos. Mechanistic studies demonstrate that pro-amniotic cavity formation and size-regulation, albeit concomitant, have distinct molecular underpinnings. While size regulation is mainly achieved through lengthening of the cell cycle, lumenogenesis is dependent on programmed cell death in double embryos. In fact, increasing epiblast size results in a multi-layered epithelium in which multiple luminal cavities arise, whose fusion is mediated by apoptosis of inner cells lacking contact with the basement membrane. Taken together, this study furthers our understanding of how embryos compensate for increased cell numbers to achieve correct size and morphology.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2019

Author dc:creator

• Orietti, Lorenzo

Advisor dc:contributor.advisor

• Zernicka-Goetz, Magdalena

• Mouse Embryos
• Mouse stem cell
• Size regulation
• Mouse Morphogenesis

Licence

• https://www.repository.cam.ac.uk/bitstreams/335ecb5d-fa8a-4963-b818-1bf90f173491/download
• http://purl.org/NET/rdflicense/allrightsreserved

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.54886

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/307794