osr1 as a Novel Marker for ICC-Like Cells Development in Zebrafish

Interstitial cells of Cajal (ICCs) are essential for maintaining normal intestinal function, and their dysfunction is closely associated with various gastrointestinal diseases. However, the developmental process of ICCs and their role in intestinal development remain unclear. In this study, we analyzed single-cell transcriptome data and found that odd-skipped-related 1 (OSR1) is expressed in the intestinal tissues of humans and zebrafish. Additionally, OSR1 expression was reduced in tissue biopsies obtained from IBD patients. To further explore the function of osr1 in intestinal development and disease, we generated transgenic lines Tg(osr1:mCherry) and Tg(osr1:eGFP). Furthermore, we found that these transgenic fish could label interstitial cells of Cajal-like cells (ICC-like cells) from 48 h post-fertilization (hpf) to adulthood. osr1-positive ICC-like cells form a network structure that envelops the intestine and coordinates its development. Moreover, mutations in osr1 lead to developmental defects in the intestine, characterized by disrupted ICC-like cells network structure, intestinal wall hypoplasia, and increased intestinal permeability, potentially mediated through the regulation of yap1. Overall, our findings indicate that osr1 acts as a novel marker gene for ICC-like cells and plays a crucial role in intestinal development.