title: Nell-1 induces acrania-like cranioskeletal deformities during mouse embryonic development.
abstract: We previously reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with craniosynostosis (CS). Nell-1 overexpression also results in premature suture closure/craniosynostosis in newborn transgenic mice. On a cellular level, increased levels of Nell-1 induce osteoblast differentiation and apoptosis. In this report, mice over-expressing Nell-1 were examined during embryonic development as well as shortly after birth for further analysis of craniofacial defects including neural tube defects (NTDs). The results demonstrated that overexpression of Nell-1 could induce acrania at relatively late gestation stage (E15.5) in mouse embryos, through massive apoptosis in calvarial osteoblasts and neural cells. The induced apoptosis was associated with an increase in Fas and Fas-L production. In addition, transgenic E15.5 and newborn transgenic mice with the CS phenotype displayed distortion of the chondrocranium associated with premature hypertrophy and increased apoptosis of chondrocytes. These findings were also verified in vitro with primary chondrocytes transduced with AdNell-1. In conclusion, Nell-1 overexpression can induce craniofacial anomalies associated with neural tube defects during embryonic development and may involve mechanisms of massive apoptosis associated with the Fas/Fas-L signaling pathway. NELL-1: used when describing the human gene; NELL-1: used when describing the human protein; Nell-1: used when describing the rodent gene; Nell-1: used when describing the rodent protein.
authors.affiliation: Dental and Craniofacial Research Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cowan
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
authors.forename: Steve
authors.initials: S
authors.lastname: Miao
authors.forename: Dale
authors.initials: D
authors.lastname: Carpenter
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D003398:Craniosynostoses / Q000235:genetics* / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D006023:Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010006:Osteoblasts / Q000502:physiology; D011247:Pregnancy
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; C513122:Nell1 protein, mouse; D009419:Nerve Tissue Proteins