Craniofacial abnormalities result from knock down of nonsyndromic clefting gene, crispld2, in zebrafish
- Authors
- Yuan, Q., Chiquet, B.T., Devault, L., Warman, M.L., Nakamura, Y., Swindell, E.C., and Hecht, J.T.
- ID
- ZDB-PUB-120815-13
- Date
- 2012
- Source
- Genesis (New York, N.Y. : 2000) 50(12): 871-881 (Journal)
- Registered Authors
- Swindell, Eric C.
- Keywords
- cleft lip and palate, CRISPLD2, zebrafish, neural crest cells, craniofacial development
- MeSH Terms
-
- Brain/abnormalities
- Cleft Lip/genetics
- Neural Crest/abnormalities
- Neural Crest/embryology
- Palate/abnormalities
- Palate/embryology
- Cleft Palate/genetics
- Amino Acid Sequence
- Animals
- Jaw/embryology
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- Gene Knockdown Techniques
- Craniofacial Abnormalities/genetics*
- Glycoproteins/genetics*
- Glycoproteins/metabolism
- Cell Adhesion Molecules/genetics*
- Cell Adhesion Molecules/metabolism
- Jaw Abnormalities/genetics
- Molecular Sequence Data
- Morpholinos
- PubMed
- 22887593 Full text @ Genesis
Nonsyndromic cleft lip and palate (NSCLP), a common birth defect, affects 4000 newborns in the US each year. Previously, we described an association between CRISPLD2 and NSCLP and showed Crispld2 expression in the murine palate. These results suggested that a perturbation in CRISPLD2 activity affects craniofacial development. Here, we describe crispld2 expression and the phenotypic consequence of its loss of function in zebrafish. crispld2 was expressed at all stages of zebrafish morphogenesis examined and localized to the rostral end by 1-day post fertilization. Morpholino knockdown of crispld2 resulted in significant jaw and palatal abnormalities in a dose dependent manner. Loss of crispld2 caused aberrant patterning of neural crest cells (NCC) suggesting that crispld2 is necessary for normal NCC formation. Altogether, we show that crispld2 plays a significant role in the development of the zebrafish craniofacies and alteration of normal protein levels disturbs palate and jaw formation. These data provide support for a role of CRISPLD2 in NSCLP.