Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders

Abstract

Mammals and birds have common embryological facial structures, and appear to employ the same molecular genetic developmental toolkit. We utilized natural variation found in bird beaks to investigate what genes drive vertebrate facial morphogenesis. We employed cross-species microarrays to describe the molecular genetic signatures, developmental signaling pathways and the spectrum of transcription factor (TF) gene expression changes that differ between cranial neural crest cells in the developing beaks of ducks, quails and chickens. Surprisingly, we observed that the neural crest cells established a species-specific TF gene expression profile that predates morphological differences between the species. A total of 232 genes were differentially expressed between the three species. Twenty-two of these genes, including Fgfr2, Jagged2, Msx2, Satb2 and Tgfb3, have been previously implicated in a variety of mammalian craniofacial defects. Seventy-two of the differentially expressed genes overlap with un-cloned loci for human craniofacial disorders, suggesting that our data will provide a valuable candidate gene resource for human craniofacial genetics. The most dramatic changes between species were in the Wnt signaling pathway, including a 20-fold up-regulation of Dkk2, Fzd1 and Wnt1 in the duck compared with the other two species. We functionally validated these changes by demonstrating that spatial domains of Wnt activity differ in avian beaks, and that Wnt signals regulate Bmp pathway activity and promote regional growth in facial prominences. This study is the first of its kind, extending on previous work in Darwin's finches and provides the first large-scale insights into cross-species facial morphogenesis.

Peregrine and saker falcon genome sequences provide insights into evolution of a predatory lifestyle

“…7) and have also gained a second copy of TGFB2 (a gene upregulated in curved beaks) and Dkk 2 (a gene related to longer and wider beaks in ducks) 20 . The two copies originated in different parts of a single ancestral gene ( Supplementary Figs.…”

“…Both species have migratory as well as sedentary populations, and understanding the genetic basis of this wide diversity could provide a valuable tool to aid their long-term conservation. 18,20,28,29 .…”

Prenatal ultrasound and molecular diagnosis elucidate the prognosis of Pfeiffer syndrome1)

“…This rare mutation appears to be universally lethal by early childhood due to upper airway obstruction or respiratory complications. The rare neonates who survive are severely affected and experience significant neurocognitive impairment mostly due to improper brain formation in the presence of craniosynostosis [ 2 ]. This mutation results in the addition of an unpaired cysteine in the III Ig-like loop which is vital for intermediate receptor dimerization.…”

“…Indeed, the ultrasonographic findings of a cloverleaf skull, proptosis and broad toes were similar to ultrasonographic findings previously reported in cases of PS involving severe FGFR2 mutations [ 2 , 4 ]. Additional prenatal ultrasound findings also included elbow ankylosis with bilateral humero-radio-ulnar synostosis, broad and deviated big toes and vertebral anomalies including sacrococcygeal eversion [ 2 ].…”

“…The remaining PS type 1 cases are caused by a mutation in FGFR1. FGFR1 and 2 are essential in fetal endochondral and membranous ossification and their role in craniosynostosis is likely due to their coexpression in the fetal skull, including the cranial sutures [ 2 ]. Testing is available in the clinical setting and because of some known genotypic-phenotypic correlation.…”