A Caltech Library Service

BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration

Macabenta, Frank and Sun, Hsuan-Te and Stathopoulos, Angelike (2022) BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration. Developmental Cell, 57 (14). pp. 1683-1693. ISSN 1534-5807. PMCID PMC9339487. doi:10.1016/j.devcel.2022.05.017.

[img] PDF (Document S1. Figures S1–S4) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


Tissue homeostasis involves the elimination of abnormal cells to avoid compromised patterning and function. Although quality control through cell competition is well studied in epithelial tissues, it is unknown if and how homeostasis is regulated in mesenchymal collectives. Here, we demonstrate that collectively migrating Drosophila muscle precursors utilize both fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signaling to promote homeostasis via anoikis, a form of cell death in response to substrate de-adhesion. Cell-cycle-regulated expression of the cell death gene head involution defective is responsible for caudal visceral mesoderm (CVM) anoikis. The secreted BMP ligand drives cell-cycle progression via a visceral mesoderm-specific cdc25/string enhancer to synchronize collective proliferation, as well as apoptosis of cells that have lost access to substrate-derived FGF. Perturbation of BMP-dependent cell-cycle progression is sufficient to confer anoikis resistance to mismigrating cells and thus facilitate invasion of other tissues. This BMP-gated cell-cycle checkpoint defines a quality control mechanism during mesenchymal collective migration.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Macabenta, Frank0000-0002-6583-3244
Stathopoulos, Angelike0000-0001-6597-2036
Additional Information:© 2022 Elsevier. Received 16 November 2021, Revised 2 May 2022, Accepted 20 May 2022, Available online 15 June 2022. We thank Norbert Perrimon for sharing fly stocks and Eileen Furlong for sharing the Biniou antibody. We are also grateful to the Stathopoulos lab members, in particular Heather Curtis, for helpful discussions and technical support. This study was supported by funding from the National Institutes of Health grant R01HD10018 to A.S. and a Baxter Postdoctoral Fellowship to F.M. Model figures were created with Author contributions: A.S. and F.M. conceived the project. F.M. planned the experimental approach. A.S. directed the project. F.M. and H.-T.S. performed all experiments and analyzed the data with input from A.S. The manuscript was written by F.M. and A.S. with input from H.-T.S. The authors declare no competing interests. Data and code availability: No large-scale datasets have been generated in this study. The raw microscopy data that support the findings of this study are available from the lead contact upon reasonable request. This study did not generate any software and code. Any additional information required to reanalyze the data shown in this paper is available from the lead contact upon request.
Funding AgencyGrant Number
Baxter Postdoctoral FellowshipUNSPECIFIED
Subject Keywords:cell migration; caudal visceral mesoderm; FGF signaling; BMP signaling; cell cycle; anoikis; cell death; decapentaplegic; tolkin
Issue or Number:14
PubMed Central ID:PMC9339487
Record Number:CaltechAUTHORS:20220705-346638000
Persistent URL:
Official Citation:Frank Macabenta, Hsuan-Te Sun, Angelike Stathopoulos, BMP-gated cell-cycle progression drives anoikis during mesenchymal collective migration, Developmental Cell, Volume 57, Issue 14, 2022, Pages 1683-1693.e3, ISSN 1534-5807,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:115335
Deposited By: George Porter
Deposited On:08 Jul 2022 22:55
Last Modified:03 Aug 2022 17:17

Repository Staff Only: item control page