An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis
University of Cincinnati / OhioLINK, 2010
Hochschulschrift
Zugriff:
Mutations in ZIC3 result in X-linked heterotaxy in humans, a syndrome consisting mainly of left-right (L-R) patterning defects, midline abnormalities, and cardiac malformations. Zic3 is highly expressed during gastrulation in the neuroectoderm and mesoderm of mouse and Xenopus laevis suggesting a conserved functional role in early development. To further investigate the mechanistic role of Zic3, loss of function analysis using morpholino antisense oligonucleotides was performed in Xenopus laevis. In Xenopus, knockdown of Zic3 expression results in randomization of Pitx2, a molecular marker of L-R patterning, at stage 23. At later stages, gut coiling and heart looping are reversed or ambiguous in 60% of morphants. These data recapitulate and extend phenotype information on loss of function in humans and mouse and demonstrate that the function of Zic3 in L-R patterning is conserved across species. Although loss of function of Zic3 in mouse results in abnormal L-R patterning and cardiac malformations, Zic3 null mice also exhibit defects in gastrulation, neural tube closure, and axial patterning, suggesting an earlier role in morphogenesis. These patterning events share a requirement for proper convergent extension (C-E) morphogenesis. Assay of characteristic C-E events in Xenopus, including blastopore closure, notochord elongation, and anterior-posterior axis length, demonstrates significant impairment in Zic3 morphants as compared to control morphants. Taken together, these results indicate that Zic3 plays a previously unrecognized role during early vertebrate development suggesting that early convergent extension defects underlie left-right asymmetry patterning defects at later stages
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An essential and highly conserved role for Zic3 in left-right patterning, gastrulation and convergent extension morphogenesis
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Autor/in / Beteiligte Person: | Cast, Ashley E. |
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Veröffentlichung: | University of Cincinnati / OhioLINK, 2010 |
Medientyp: | Hochschulschrift |
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