Human NELL-1 expressed in unilateral coronal synostosis

Surgical correction of unilateral coronal synostosis offers a unique opport unity to examine the molecular differences between an abnormal and a normal cranial suture, We isolated and identified a cDNA fragment whose expressio n was up-regulated in the premature fusing and fused coronal sutures, as co mpared with normal coronal sutures. The nucleotide sequence of the full-len gth cDNA of this gene, human NELL-1, has -61% homology with the chicken Nel gene. Both chicken Nel and human NELL-1 are comprised of six epidermal gro wth factor-like repeats. The human NELL-1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along th e parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion, Human multiorgan ti ssue mRNA blot showed that NELL-1 was specifically expressed in fetal brain but not in fetal kidney, liver, or lung. We also showed that Nell-1 was ex pressed in rat calvarial osteoprogenitor cells and was largely absent in ra t tibiae and fibroblast cell cultures. In conclusion, our data suggest that the NELL-1 gene is preferentially expressed in cranial intramembranous bon e and neural tissue (both of neural crest cell origin) and is up-regulated during unilateral premature closure of the coronal suture, The precise role of this gene is unknown.