학술논문

Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor
Document Type
article
Source
Stem Cell Reports. 16(6)
Subject
Biochemistry and Cell Biology
Biological Sciences
Digestive Diseases
Stem Cell Research - Nonembryonic - Non-Human
Regenerative Medicine
Stem Cell Research
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Aging
Animals
Cell Adhesion Molecules
Neuronal
Cell Proliferation
Drosophila
Drosophila Proteins
ErbB Receptors
Female
Gene Expression Regulation
Developmental
Intestines
Signal Transduction
Stem Cells
EGFR
L1CAM
Neuroglian
aging
intestine
Clinical Sciences
Biochemistry and cell biology
Language
Abstract
The Drosophila intestine is an excellent system for elucidating mechanisms regulating stem cell behavior. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and enteroblasts (EBs) within the fly intestine. SJs are not present between ISCs and EBs, suggesting Nrg plays a different role in this tissue. We reveal that Nrg is required for ISC proliferation in young flies, and depletion of Nrg from ISCs and EBs suppresses increased ISC proliferation in aged flies. Conversely, overexpression of Nrg in ISC and EBs promotes ISC proliferation, leading to an increase in cells expressing ISC/EB markers; in addition, we observe an increase in epidermal growth factor receptor (Egfr) activation. Genetic epistasis experiments reveal that Nrg acts upstream of Egfr to regulate ISC proliferation. As Nrg function is highly conserved in mammalian systems, our work characterizing the role of Nrg in the intestine has implications for the treatment of intestinal disorders that arise due to altered ISC behavior.