Biology subjects

Daube, M.

Publications and source records attributed to Daube, M..

3 recordsLinked to original sources

bioRxiv2026

Conserved role of EGFR signaling in apoptotic cell recognition and processing across different phagocytes

Efferocytosis is an essential process that clears dying cells from tissues and prevents inflammation. However, the mechanisms by which apoptotic cells recruit and activate phagocytes remain poorly understood. Here, we show that EGFR signaling is both necessary and sufficient for efficient efferocytosis in two diverse phagocytes: the gonadal sheath cells of C. elegans and the zebrafish microglia. In C. elegans, loss of LET-23 EGFR or its downstream effector MPK-1 ERK in the sheath cells impairs the recognition and degradation of apoptotic germ cells. Germ cells undergoing apoptosis secrete the EGF ligand LIN-3, which promotes their recognition and engulfment. Overexpression of EGF in non-apoptotic germ cells is sufficient to trigger their engulfment, indicating that EGF can function as an engulfment signal independently of apoptotic cell death. In zebrafish larvae, pharmacological inhibition of EGFR signaling reduces microglial motility, recognition of apoptotic neurons, and corpse clearance in the optic tectum. Similar to C. elegans, an ectopic source of EGF serves as an attractive cue that promotes microglial recruitment. Our findings suggest that EGFR signaling controls an evolutionarily conserved efferocytosis module that coordinates the recognition and processing of apoptotic corpses in different types of phagocytes.

cell biology↗

bioRxiv2021

A DNA Replication-Independent Function of the pre-Replication Complex during Cell Invasion in C. elegans

Cell invasion is an initiating event during tumor cell metastasis and an essential process during development. A screen of C. elegans orthologs of genes over-expressed in invasive human melanoma cells has identified several components of the conserved DNA pre-replication complex (pre-RC) as positive regulators of anchor cell (AC) invasion. The pre-RC functions cell-autonomously in the G1-arrested AC to promote invasion, independently of its role in licensing DNA replication origins in proliferating cells. While the helicase activity of the pre-RC is necessary for AC invasion, the downstream acting DNA replication initiation factors are not required. The pre-RC promotes the invasive fate by regulating the expression of extracellular matrix genes and components of the PI3K signaling pathway. Increasing PI3K pathway activity partially suppressed the AC invasion defects caused by pre-RC depletion, suggesting that the PI3K pathway is one critical pre-RC target. We propose that the pre-RC acts in the non-proliferating AC as a transcriptional regulator that facilitates the switch to an invasive phenotype.

cell biology↗

bioRxiv2019

The C. elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.\n\nAnchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation.\n\nTaken together, our data have identified egl-43 Evi1 as a critical factor coordinating cell invasion with cell cycle arrest.\n\nAuthor summaryCells invasion is a fundamental biological process that allows cells to cross compartment boundaries and migrate to new locations. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.\n\nWe have investigated how a specialized cell in the Nematode C. elegans, the so-called anchor cell, can invade into an adjacent epithelium. Our work has identified an oncogenic transcription factor that controls the expression of specific target genes necessary for cell invasion, and at the same time inhibits the proliferation of the invading anchor cell.\n\nThese findings shed light on the mechanisms, by which cells decide whether to proliferate or invade.

developmental biology↗