PUBLICATION

Wtip and Vangl2 are required for mitotic spindle orientation and cloaca morphogenesis

Authors
Bubenshchikova, E., Ichimura, K., Fukuyo, Y., Powell, R., Hsu, C., Morrical, S.O., Sedor, J.R., Sakai, T., and Obara, T.
ID
ZDB-PUB-121210-8
Date
2012
Source
Biology Open   1(6): 588-596 (Journal)
Registered Authors
Obara, Tomoko
Keywords
ciliopathies, mitotic spindle, basal body, zebrafish
MeSH Terms
none
PubMed
23213452 Full text @ Biol. Open
Abstract

Defects in cilia and basal bodies function are linked to ciliopathies, which result in kidney cyst formation. Recently, cell division defects have been observed in cystic kidneys, but the underlying mechanisms of such defects remain unclear. Wtip is an LIM domain protein of the Ajuba/Zyxin family, but its role in ciliogenesis during embryonic development has not been previously described. We report Wtip is enriched in the basal body and knockdown of wtip leads to pronephric cyst formation, cloaca malformation, hydrocephalus, body curvature, and pericardial edema. We additionally show that wtip knockdown embryos display segment-specific defects in the pronephros: mitotic spindle orientation defects are observed only in the anterior and middle pronephros; cloaca malformation is accompanied by a reduced number of ciliated cells; and ciliated cells lack the striated rootlet that originates from basal bodies, which results in a lack of cilia motility. Our data suggest that loss of Wtip function phenocopies Vangl2 loss of function, a core planar cell polarity (PCP) protein located in the basal body protein. Furthermore, we demonstrate that wtip and vangl2 interact genetically. Taken together, our results indicate that in zebrafish, Wtip is required for mitotic spindle orientation in the anterior and middle of the pronephros, cloaca morphogenesis, and PCP, which may underlie the molecular etiology of ciliopathies.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping