Klf5a in Endoderm Promotes Pharyngeal Cartilage Morphogenesis

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 <i>klf5a</i>, a zinc-finger transcription factor expressed in pharyngeal endodermal pouches, in zebrafish pharyngeal cartilage development. Knockdown of <i>klf5a</i> using morpholinos minimally affected cranial NCC specification and migration but significantly impaired their proliferation and differentiation in the pharyngeal region. Notably, <i>klf5a</i> deficiency reduced expression of <i>fgfbp2b</i>, a modulator of FGF signaling, in the pharyngeal endoderm. Co-injection of <i>klf5a</i> mRNA rescued the cartilage defects, but injection of <i>fgfbp2b</i> mRNA alone failed to restore normal cartilage morphogenesis, suggesting that <i>fgfbp2b</i> is not the sole mediator of <i>klf5a</i>'s effects. These findings indicate that <i>klf5a</i> regulates endodermal signaling to direct NCC-derived pharyngeal cartilage formation, likely through multiple downstream targets including <i>fgfbp2b</i>. This study provides insights into the complex molecular network underlying craniofacial development and highlights potential therapeutic targets for craniofacial disorders.