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Surgical correction of unilateral coronal synostosis offers a unique opportunity to examine the molecular differences between an abnormal and a normal cranial suture. We isolated and identified a cDNA fragment whose expression was up‐regulated in the premature fusing and fused coronal sutures, as compared with normal coronal sutures. The nucleotide sequence of the full‐length 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 growth factor‐like repeats. The human NELL‐1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion. Human multiorgan tissue mRNA blot showed that NELL‐1 was specifically expressed …