title: Craniofacial abnormalities result from knock down of nonsyndromic clefting gene, crispld2, in zebrafish.
abstract: Nonsyndromic cleft lip and palate (NSCLP), a common birth defect, affects 4,000 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 postfertilization. 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.
authors.affiliation: Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Yuan
authors.forename: Brett T
authors.initials: BT
authors.lastname: Chiquet
authors.forename: Laura
authors.initials: L
authors.lastname: Devault
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Warman
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Eric C
authors.initials: EC
authors.lastname: Swindell
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Hecht
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000002:abnormalities; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002971:Cleft Lip / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D007568:Jaw / Q000196:embryology; D007569:Jaw Abnormalities / Q000235:genetics; D008969:Molecular Sequence Data; D060172:Morpholinos; D009432:Neural Crest / Q000002:abnormalities / Q000196:embryology; D010159:Palate / Q000002:abnormalities / Q000196:embryology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C581700:CRISPLD2 protein, zebrafish; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D060172:Morpholinos; D029961:Zebrafish Proteins