Work

Hipk Is a Critical Mediator of Stress-Induced Intestinal Hyperplasia via the Hippo Pathway in Drosophila

Year: 2026

Type: article

Abstract: The Drosophila midgut serves as a powerful model system for studying the mechanisms underlying stem cell hyperproliferation induced by gut damage and Yorkie (Yki) activation. Homeodomain-interacting protein kinase (Hipk) has recently been shown to regulate intestinal stem cell (ISC) proliferation and differentiation during normal homeostasis. Here, we show that Hipk is cell-autonomously required for ISC hyperproliferation stimulated by both gut damage and Yki activation. Progenitor-specific hipk knockdown abolished the ISC hyperproliferation and gut hyperplasia induced by dextran sulfate sodium (DSS)-mediated injury and Yki overexpression. Mechanistically, Hipk promotes Yki protein stability and nuclear accumulation in progenitors. This regulation is specific to wild-type Yki, as the constitutively active YkiS168A mutant, which escapes Warts-mediated inhibition, is insensitive to Hipk depletion. These findings identify Hipk as a critical regulator of Yki activation during ISC hyperproliferation.

Source: Biology

DOI: 10.3390/biology15131029

Authors: Xiaojie Wu, Hyung Chul Lee, Changsoo Kim

Institution: Chonnam National University

Language: English

Topic: Hippo pathway signaling and YAP/TAZ

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258