Zebrafish study maps genome-wide transcriptional changes underlying adaptation to protein malnutrition

A study published in PLOS Genetics by Siyao Wang, Laura Childers, Fernando Martinez III, Michel Bagnat, Jieun Park, and colleagues describes genome-wide transcriptional changes that allow zebrafish to adapt gradually and repeatedly to severe protein malnutrition caused by loss of Plasmolipin (pllp) function.

Plasmolipin is an endosomal membrane protein highly expressed in lysosome-rich enterocytes (LREs) — a specialised population of intestinal cells that mediate dietary protein uptake in fish and neonatal mammals. Loss of pllp impairs LRE differentiation and protein absorption, normally resulting in poor growth and markedly reduced survival. The team found that homozygous pllp mutant zebrafish that do survive undergo coordinated, reproducible transcriptional reprogramming, identifying gene networks involved in adaptive responses to nutritional stress.

The findings contribute to understanding how intestinal cells respond to protein malnutrition at the molecular level and may inform future research on LRE biology relevant to neonatal nutrition and intestinal disease in mammals. The study is published as a peer-reviewed article and is therefore not subject to the caveats that apply to preprint material.