Biology subjects

Van Hazel, C.

Publications and source records attributed to Van Hazel, C..

3 recordsLinked to original sources

bioRxiv2025

Asperous coordinates regenerative timing by regulating damage-induced WNT Signaling

Tissue regeneration requires precise control of signaling pathways to direct proliferation, differentiation, and patterning. While early responses to injury are well characterized, how differentiation is coordinated during later stages remains unclear. Here, we identify Asperous (Aspr), an EGF-repeat protein, as a regeneration-specific regulator in Drosophila wing discs. Aspr is dispensable for wing development but is strongly induced within 24 hours post-injury. Maintaining aspr expression inhibits differentiation and alters reparative growth, while loss impairs regeneration. Structural and expression analyses show Aspr is an extracellular protein secreted in extracellular vesicles (EVs), where it co-localizes with the WNT ligand Wingless (Wg). We find Aspr regulates post-injury but not developmental Wg signaling, potentially by influencing its secretion or availability via EVs. These findings suggest Aspr regulates WNT activity to ensure proper timing of cell fate specification during regeneration, revealing a mechanism by which signaling dynamics are temporally controlled during tissue repair.

developmental biology↗

bioRxiv2024

A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration

Tissue regeneration requires precise activation and coordination of genes, many of which are reused from development. While key factors have been identified, how their expression is initiated and spatially regulated after injury remains unclear. The stress-activated MAP kinase JNK is a conserved driver of regeneration and promotes expression of genes involved in proliferation, growth, and cell fate changes in Drosophila. However, how JNK selectively activates its targets in damaged tissue is not well understood. We previously identified Damage-Responsive, Maturity-Silenced (DRMS) enhancers as JNK-activated elements critical for regeneration. Here, we show that cell death is dispensable for the activation of these enhancers, which only depends on JNK and its immediate downstream effectors. One of these is JAK/STAT, which acts as a direct, additional input necessary to expand enhancer activity into the wound periphery where JNK alone is insufficient. Furthermore, we demonstrate that a threshold level of JNK is required to initiate enhancer activation. Together, our findings reveal how JNK and JAK/STAT signaling cooperate to drive spatially and temporally regulated gene expression through damage-responsive enhancers, ensuring proper regenerative outcomes.

genetics↗

bioRxiv2024

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of necrosis and how it impacts surrounding healthy tissue - an essential consideration when developing effective methods to treat such injuries - has been limited by a lack of robust genetically tractable models. Our lab previously established a method to study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed a unique phenomenon whereby cells at a distance from the injury upregulate caspase activity in a process called Necrosis-induced Apoptosis (NiA) that is vital for regeneration. Here we have further investigated this phenomenon, showing that NiA is predominantly associated with the highly regenerative pouch region of the disc, shaped by genetic factors present in the presumptive hinge. Furthermore, we find that a proportion of NiA fail to undergo apoptosis, instead surviving effector caspase activation to persist within the tissue and stimulate reparative proliferation late in regeneration. This proliferation relies on the initiator caspase Dronc, and occurs independent of JNK, ROS or mitogens associated with the previously characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal a new means by which non-apoptotic Dronc signaling promotes regenerative proliferation in response to necrotic damage.

genetics↗