HOXC10 intronic duplication is associated with unsealed skull and crest in crested chicken with cerebral hernia.

The genetic basis and developmental mechanism of unsealed skull in crested chicken with cerebral hernia remain unclear. Here, a genomic region including six HOXC genes was mapped by bulked segregant analysis (BSA) in a crested chicken resource population. A 195-bp intronic tandem duplication was further confirmed in the HOXC10 gene. HOXC genes, particularly HOXC10, were expressed ectopically in fetal skin and meningeal tissues of crested chicken with cerebral hernia, indicating its impact on the cranial mesenchymal tissues that drive the development of scalp skin, frontal bone, and meninges. The restricted expansion of frontal bone progenitors labeled with anti-RUNX2 antibody in the supraorbital mesenchyme of the fetal head implied abnormal migration, which contributed to the formation of the unsealed skull. This study suggests that HOXC genes were potent drivers for the abnormalities of the head crest and unsealed skull observed in crested chicken with cerebral hernia.