Biology subjects

Ratheesh, A.

Publications and source records attributed to Ratheesh, A..

3 recordsLinked to original sources

bioRxiv2024

N-Cadherin mediated cell rearrangements shape embryonic macrophage cluster

Drosophila embryonic macrophages are highly motile phagocytic and secretory cells which are essential for embryonic development. Embryonic migration and dispersal of these cells along pre-determined routes is invariably tied to their functions such that misrouting or delay in macrophage migration has serious consequences for embryogenesis and adult homeostasis. In this study, we describe early steps of macrophage migration from their site of origin in the head mesoderm to the germband and show that hemocytes start moving as an epithelial-like cluster with N-Cadherin based Adherens junctions. The cells within the cluster move in a co-ordinated manner and exhibit cell rearrangements mediated through junction shrinkage. We found that N-Cadherin is dynamically relocalized during cluster extension and modulating N-Cadherin levels results in hemocyte dispersal away from their main axis of migration which affects migration into the germband. We therefore elucidate a novel multi-tiered mechanism which ensures that macrophages are positioned appropriately to regulate their distribution in the embryo.

developmental biology↗

bioRxiv2021

Cell division in tissues enables macrophage infiltration

Migration of cells through diverse tissues is essential for development, immune response and cancer metastasis 1-3. To reach their destination, cells must overcome the resistance imposed by complex microenvironments, composed of neighboring cells and extracellular matrix (ECM)4-6. While migration through pores and tracks in ECM has been well studied 4,5,7, little is known about cellular traversal into confining cell-dense tissues. Here by combining quantitative live imaging with genetic and optogenetic perturbations we identify a crucial role for cell division during cell migration into tissues. We find that normal embryonic invasion by Drosophila macrophages between the ectoderm and mesoderm8,9 absolutely requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by Integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade. Decreasing or increasing the frequency of ectodermal division correspondingly either hinders or promotes macrophage invasion. Reducing the levels of focal adhesion components in the ectoderm allows macrophage entry even in the absence of division. Our study demonstrates the critical importance of division at the entry site to enable in vivo cell invasion by relieving the steric impediment caused by focal adhesions. We thus provide a new perspective on the regulation of cellular movement into tissues.

cell biology↗

bioRxiv2018

A conserved MFS orchestrates a subset of O-glycosylation to facilitate macrophage dissemination and tissue invasion

Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on protein pathways previously linked to cancer, most strongly on the protein sulfhydryl oxidase Qsox1 which we show is required for macrophage invasion. Minervas vertebrate ortholog, MFSD1, rescues the minerva mutants migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.

cancer biology↗