eprintid: 10141376
rev_number: 12
eprint_status: archive
userid: 608
dir: disk0/10/14/13/76
datestamp: 2022-01-07 11:54:50
lastmod: 2022-01-07 11:54:50
status_changed: 2022-01-07 11:54:50
type: article
metadata_visibility: show
creators_name: Hoijman, E
creators_name: Häkkinen, H-M
creators_name: Tolosa-Ramon, Q
creators_name: Jiménez-Delgado, S
creators_name: Wyatt, C
creators_name: Miret-Cuesta, M
creators_name: Irimia, M
creators_name: Callan-Jones, A
creators_name: Wieser, S
creators_name: Ruprecht, V
title: Cooperative epithelial phagocytosis enables error correction in the early embryo
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: F99
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Errors in early embryogenesis are a cause of sporadic cell death and developmental failure1,2. Phagocytic activity has a central role in scavenging apoptotic cells in differentiated tissues3-6. However, how apoptotic cells are cleared in the blastula embryo in the absence of specialized immune cells remains unknown. Here we show that the surface epithelium of zebrafish and mouse embryos, which is the first tissue formed during vertebrate development, performs efficient phagocytic clearance of apoptotic cells through phosphatidylserine-mediated target recognition. Quantitative four-dimensional in vivo imaging analyses reveal a collective epithelial clearance mechanism that is based on mechanical cooperation by two types of Rac1-dependent basal epithelial protrusions. The first type of protrusion, phagocytic cups, mediates apoptotic target uptake. The second, a previously undescribed type of fast and extended actin-based protrusion that we call 'epithelial arms', promotes the rapid dispersal of apoptotic targets through Arp2/3-dependent mechanical pushing. On the basis of experimental data and modelling, we show that mechanical load-sharing enables the long-range cooperative uptake of apoptotic cells by multiple epithelial cells. This optimizes the efficiency of tissue clearance by extending the limited spatial exploration range and local uptake capacity of non-motile epithelial cells. Our findings show that epithelial tissue clearance facilitates error correction that is relevant to the developmental robustness and survival of the embryo, revealing the presence of an innate immune function in the earliest stages of embryonic development.
date: 2021-02-25
date_type: published
official_url: https://doi.org/10.1038/s41586-021-03200-3
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1854208
doi: 10.1038/s41586-021-03200-3
pii: 10.1038/s41586-021-03200-3
lyricists_name: Wyatt, Christopher
lyricists_id: CDRWY41
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Nature
volume: 590
number: 7847
pagerange: 618-623
event_location: England
citation:        Hoijman, E;    Häkkinen, H-M;    Tolosa-Ramon, Q;    Jiménez-Delgado, S;    Wyatt, C;    Miret-Cuesta, M;    Irimia, M;             ... Ruprecht, V; + view all <#>        Hoijman, E;  Häkkinen, H-M;  Tolosa-Ramon, Q;  Jiménez-Delgado, S;  Wyatt, C;  Miret-Cuesta, M;  Irimia, M;  Callan-Jones, A;  Wieser, S;  Ruprecht, V;   - view fewer <#>    (2021)    Cooperative epithelial phagocytosis enables error correction in the early embryo.                   Nature , 590  (7847)   pp. 618-623.    10.1038/s41586-021-03200-3 <https://doi.org/10.1038/s41586-021-03200-3>.       Green open access   
 
document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10141376/1/Hoi_Nat_Co.pdf