Biology subjects

Kango-Singh, M.

Publications and source records attributed to Kango-Singh, M..

3 recordsLinked to original sources

bioRxiv2026

A Genetic Mechanism Linking Hippo Signaling to Dorsoventral Patterning for Control of Head and Eye Development

The integration of growth and patterning in developing tissues is a complex process involving both intrinsic and extrinsic cues. The Hippo pathway, a conserved regulator of organ size, controls growth and patterning in Drosophila, including the development of the eye-antennal imaginal disc into adult structures. Defective Proventriculus (Dve), a SATB1/2 ortholog and K-50 type transcription factor regulates dorsal-ventral (DV) patterning during Drosophila eye development. Dve works with Wingless (Wg) to suppress eye development and promote head cuticle fate, thereby influencing the positioning of eyes and interocular distance. Our study investigates the role of the Hippo effector Yorkie (Yki), and dve in coordinating growth and patterning during eye development, specifically focusing on the regulation of the head cuticle domain. Here we show that Hippo signaling, mediated by Yki, regulates the size of the head cuticle domain and morphogenetic furrow (MF) progression, and that Dve suppresses Yki activity in the dorsal head region. Furthermore, Yki regulates several DV patterning genes like pnr, wg and mirr, to coordinate eye and head development. Mutations in mammalian orthologs of yki, dve, pnr and wg are associated with facial dysmorphia and several developmental disorders. Our studies thus reveal new genetic mechanisms by which growth and patterning are coordinated for head and eye development across species.

developmental biology↗

bioRxiv2023

A Tumour-Specific Molecular Network Promotes Tumour Growth in Drosophila by Enforcing a JNK-YKI Feedforward Loop

Cancer cells expand rapidly in response to altered intercellular and signalling interactions to achieve hallmarks of cancer. Impaired cell polarity combined with activated oncogenes is known to promote several hallmarks of cancer e.g., activating invasion by increased activity of Jun N-terminal kinase (JNK), and sustained proliferative signalling by increased activity of Hippo effector Yorkie (Yki). Thus, JNK, Yki, and their downstream transcription factors have emerged as synergistic drivers of tumour growth through pro-tumour signalling and intercellular interactions like cell-competition. However, little is known about the signals that converge onto JNK and Yki in tumour cells that enable the tumour cells to achieve hallmarks of cancer. Here, using mosaic models of cooperative oncogenesis (RasV12, scrib-) in Drosophila, we show that RasV12, scrib- tumour cells grow by activation of a previously unidentified network comprising Wingless (Wg), Dronc, JNK and Yki. We show that RasV12, scrib- cells show increased Wg, Dronc, JNK, and Yki signalling, and all of these signals are required for the growth of RasV12, scrib- tumours. We report that Wg and Dronc converge onto a JNK-Yki self-reinforcing positive feedback signal-amplification loop that promotes tumour growth. We found that Wg-Dronc-Yki-JNK molecular network is specifically activated in polarity-impaired tumour cells and not in normal cells where apical basal polarity is intact. Our findings suggest that identification of molecular networks may provide significant insights about the key biologically meaningful changes in signalling pathways, and paradoxical signals that promote Tumourigenesis.

cancer biology↗

bioRxiv2020

THE YKI-CACTUS(IKBα)-JNK AXIS PROMOTES TUMOR GROWTH AND PROGRESSION IN DROSOPHILA

Presence of inflammatory factors in the tumor microenvironment is well known yet their specific role in tumorigenesis is elusive. The core inflammatory pathways are conserved in Drosophila, including the Toll-Like Receptor (TLR) and the Tumor Necrosis Factor (TNF) pathway. We used Drosophila tumor models to study the role of inflammatory factors in tumorigenesis. Specifically, we co-activated oncogenic forms of RasV12 or its major effector Yorkie (Yki3SA) in polarity deficient cells mutant for tumor suppressor gene scribble (scrib) marked by GFP under nubGAL4 or in somatic clones. This system recapitulates the clonal origins of cancer, and shows neoplastic growth, invasion and lethality. We investigated if TLR and TNF pathway affect growth of Yki3SAscribRNAi or RasV12scribRNAi tumors through activation of tumor promoting Jun N-terminal Kinase (JNK) pathway and its target Matrix Metalloprotease1 (MMP1). We report, TLR component, Cactus (Cact) is highly upregulated in Yki3SAscribRNAi or RasV12scribRNAi tumors. Drosophila Cactus (mammalian IKB) acts as an inhibitor of NFKB signaling that plays key roles in inflammatory and immune response. Here we show an alternative role for Cactus, and by extension cytokine mediated signaling, in tumorigenesis. Downregulating Cact affects both tumor progression and invasion. Interestingly, downregulating TNF receptors in tumor cells did not affect their invasiveness despite reducing JNK activity. Genetic analysis suggested that Cact and JNK are key regulators of tumor progression. Overall, we show that Yki plays a critical role in tumorigenesis by controlling Cact, which in turn, mediates tumor promoting JNK oncogenic signaling in tumor cells.

cancer biology↗