# Klf5a in Endoderm Promotes Pharyngeal Cartilage Morphogenesis

## TL;DR

The gene klf5a in zebrafish endoderm helps form throat cartilage by regulating signals that control cell growth and specialization.

## Contribution

This study identifies klf5a as a key regulator of pharyngeal cartilage development through endoderm-derived signaling.

## Key findings

- Klf5a knockdown impairs neural crest cell proliferation and differentiation in the pharyngeal region.
- Klf5a regulates fgfbp2b expression in the endoderm, but fgfbp2b alone cannot rescue cartilage defects.
- Klf5a mRNA rescues cartilage defects, indicating its direct role in cartilage morphogenesis.

## Abstract

Pharyngeal cartilage, derived from neural crest cells (NCCs), undergoes complex morphogenesis driven by signals from the pharyngeal endoderm. However, the molecular mechanisms governing NCC proliferation and differentiation in response to endoderm-derived signals remain poorly understood. Here, we investigate the role of klf5a, a zinc-finger transcription factor expressed in pharyngeal endodermal pouches, in zebrafish pharyngeal cartilage development. Knockdown of klf5a using morpholinos minimally affected cranial NCC specification and migration but significantly impaired their proliferation and differentiation in the pharyngeal region. Notably, klf5a deficiency reduced expression of fgfbp2b, a modulator of FGF signaling, in the pharyngeal endoderm. Co-injection of klf5a mRNA rescued the cartilage defects, but injection of fgfbp2b mRNA alone failed to restore normal cartilage morphogenesis, suggesting that fgfbp2b is not the sole mediator of klf5a’s effects. These findings indicate that klf5a regulates endodermal signaling to direct NCC-derived pharyngeal cartilage formation, likely through multiple downstream targets including fgfbp2b. This study provides insights into the complex molecular network underlying craniofacial development and highlights potential therapeutic targets for craniofacial disorders.