# Lgr5⁺ cells regulate small intestinal morphogenesis before villification

## TL;DR

This study shows that Lgr5⁺ cells in the embryonic small intestine control morphogenesis through region-specific stemness and Hedgehog signaling.

## Contribution

The study reveals the functional roles and stemness properties of embryonic Lgr5⁺ cells prior to villification.

## Key findings

- PVLCs exhibit region-specific stemness with enhanced potential from proximal to distal regions.
- PVLCs regulate intestinal morphogenesis via Hedgehog signaling in a region-dependent manner.
- Distal morphogenesis is more reliant on Hedgehog signaling from PVLCs.

## Abstract

Lgr5 marks both adult intestinal stem cells and embryonic intestinal stem/progenitor cells. However, the stemness properties and physiological roles of embryonic intestinal Lgr5⁺ cells prior to villification (PVLCs) remain largely unknown. In this study, we show that PVLCs in the embryonic small intestine exhibit region-specific stemness, with progressively enhanced stemness potential from the proximal to distal region. Through inducible cell ablation and gene knockout experiments, we demonstrate that PVLCs regulate small intestinal morphogenesis via Hedgehog signaling in a region-dependent manner, with distal morphogenesis being more dependent on this mechanism. This study reveals the stemness and functional roles of PVLCs in the embryonic small intestine prior to villification, highlighting regionalized cellular heterogeneity as a critical determinant of intestinal morphogenesis.

The online version contains supplementary material available at 10.1186/s13619-026-00284-y.