PUBLICATION
An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis
- Authors
- Cast, A.E., Gao, C., Amack, J.D., and Ware, S.M.
- ID
- ZDB-PUB-120202-3
- Date
- 2012
- Source
- Developmental Biology 364(1): 22-31 (Journal)
- Registered Authors
- Amack, Jeffrey, Gao, Chunlei
- Keywords
- convergent extension, left-right patterning, heterotaxy, axis formation, cardiovascular malformation
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Body Patterning*
- Embryo, Nonmammalian/metabolism
- Female
- Gastrulation*
- Gene Expression Regulation, Developmental*
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Male
- Transcription Factors/deficiency
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Xenopus Proteins/deficiency
- Xenopus Proteins/metabolism*
- Xenopus laevis/embryology*
- Xenopus laevis/genetics
- Xenopus laevis/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 22285814 Full text @ Dev. Biol.
Citation
Cast, A.E., Gao, C., Amack, J.D., and Ware, S.M. (2012) An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis. Developmental Biology. 364(1):22-31.
Abstract
Mutations in ZIC3 result in X-linked heterotaxy in humans, a syndrome consisting of left–right (L–R) patterning defects, midline abnormalities, and cardiac malformations. Similarly, loss of function of Zic3 in mouse results in abnormal L–R patterning and cardiac development. However, Zic3 null mice also exhibit defects in gastrulation, neural tube closure, and axial patterning, suggesting the hypothesis that Zic3 is necessary for proper convergent extension (C-E) morphogenesis. To further investigate the role of Zic3 in early embryonic development, we utilized two model systems, Xenopus laevis and zebrafish, and performed loss of function analysis using antisense morpholino-mediated gene knockdown. Both Xenopus and zebrafish demonstrated significant impairment of C-E in Zic3 morphants. L–R patterning was also disrupted, indicating that the role of Zic3 in L–R axis development is conserved across species. Correlation of L–R patterning and C-E defects in Xenopus suggests that early C-E defects may underlie L–R patterning defects at later stages, since Zic3 morphants with moderate to severe C-E defects exhibited an increase in laterality defects. Taken together, these results demonstrate a functional conservation of Zic3 in L–R patterning and uncover a previously unrecognized role for Zic3 in C-E morphogenesis during early vertebrate development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping