Since a global Nell-1 expression model partially rescued the CCD phenotype in Runx2+/− mice, to further confirm that the observed partial rescue of the CCD phenotype in vivo is attributable to Nell-1 activity in osteoblastic cell lineages, calvarial explants from Runx2+/− and Runx2−/− newborn mice were cultured in the presence (Fig. 4A–C, G) or absence (Fig. 4D–F, H) of recombinant (r)Nell-1 to create an environment without systemic influences. Here, NELL1 is linked to cleidocranial dysplasia 1.