DOI: 10.1242/dev.201958 ISSN: 0950-1991

An EMC-Hpo-Yki axis maintains intestinal homeostasis under physiological and pathological conditions

Lin Shi, Hubing Ma, Jinjun Wang, Meifang Ma, Hang Zhao, Zhengran Li, Jian-Hua Wang, Shian Wu, Zizhang Zhou, Meng-qiu Dong, Zhouhua Li
  • Developmental Biology
  • Molecular Biology

Balanced control of stem cell proliferation and differentiation underlines tissue homeostasis. Disruption of tissue homeostasis often results in many diseases. However, how endogenous factors influence the proliferation and differentiation of intestinal stem cells (ISCs) under physiological and pathological conditions remains not fully understood. Here, we find that the evolutionarily conserved endoplasmic reticulum membrane protein complex (EMC) negatively regulates ISC proliferation and intestinal homeostasis. Compromising EMC function in progenitors leads to excessive ISC proliferation and intestinal homeostasis disruption. Mechanistically, EMC associates with and stabilizes Hippo (Hpo) protein, the key component of the Hpo signaling pathway. In the absence of EMC, Yorkie (Yki) is activated to promote ISC proliferation due to Hpo destruction. The EMC-Hpo-Yki axis also functions in enterocytes to maintain intestinal homeostasis. Importantly, the levels of EMC are dramatically diminished in tunicamycin (TM)-treated animals, leading to Hpo destruction, thereby resulting in intestinal homeostasis disruption due to Yki activation. Thus, our study uncovers the molecular mechanism of EMC in intestinal homeostasis maintenance under physiological and pathological conditions and provide new insight into the pathogenesis of TM-induced tumorigenesis.

More from our Archive