Zic3 is involved in the left-right specification of the Xenopus embryo

T. Kitaguchi, T. Nagai, K. Nakata, J. Aruga, K. Mikoshiba

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Establishment of left-right (L-R) asymmetry is fundamental to vertebrate development. Several genes involved in L-R asymmetry have been described. In the Xenopus embryo, Vg1/activin signals are implicated upstream of asymmetric nodal related 1 (Xnr1) and Pitx2 expression in L-R patterning. We report here that Zic3 carries the left-sided signal from the initial activin-like signal to determinative factors such as Pitx2. Overexpression of Zic3 on the right side of the embryo altered the orientation of heart and gut looping, concomitant with disturbed laterality of expression of Xnr1 and Pitx2, both of which are normally expressed in the left lateral plate mesoderm. The results indicate that Zic3 participates in the left-sided signaling upstream of Xnr1 and Pitx2. At early gastrula, Zic3 was expressed not only in presumptive neuroectoderm but also in mesoderm. Correspondingly, overexpression of Zic3 was effective in the L-R specification at the early gastrula stage, as revealed by a hormone-inducible Zic3 construct. The Zic3 expression in the mesoderm is induced by activin β or Vg1, which are also involved in the left-sided signal in L-R specification. These findings suggest that an activin-like signal is a potent upstream activator of Zic3 that establishes the L-R axis. Furthermore, overexpression of the zinc-finger domain of Zic3 on the right side is sufficient to disturb the L-R axis, while overexpression of the N-terminal domain on the left side affects the laterality. These results suggest that Zic3 has at least two functionally important domains that play different roles and provide a molecular basis for human heterotaxy, which is an L-R pattern anomaly caused by a mutation in human ZIC3.

Original languageEnglish
Pages (from-to)4787-4795
Number of pages9
JournalDevelopment
Volume127
Issue number22
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Activins
Xenopus
Mesoderm
Embryonic Structures
Gastrula
Neural Plate
Zinc Fingers
Vertebrates
Hormones
Mutation
Genes

Keywords

  • Activin
  • Heterotaxy
  • Left-right asymmetry
  • Left-right axis determination
  • Pitx2
  • Vgl
  • Xenopus
  • Xnrl
  • Zic3

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Kitaguchi, T., Nagai, T., Nakata, K., Aruga, J., & Mikoshiba, K. (2000). Zic3 is involved in the left-right specification of the Xenopus embryo. Development, 127(22), 4787-4795.

Zic3 is involved in the left-right specification of the Xenopus embryo. / Kitaguchi, T.; Nagai, T.; Nakata, K.; Aruga, J.; Mikoshiba, K.

In: Development, Vol. 127, No. 22, 2000, p. 4787-4795.

Research output: Contribution to journalArticle

Kitaguchi, T, Nagai, T, Nakata, K, Aruga, J & Mikoshiba, K 2000, 'Zic3 is involved in the left-right specification of the Xenopus embryo', Development, vol. 127, no. 22, pp. 4787-4795.
Kitaguchi T, Nagai T, Nakata K, Aruga J, Mikoshiba K. Zic3 is involved in the left-right specification of the Xenopus embryo. Development. 2000;127(22):4787-4795.
Kitaguchi, T. ; Nagai, T. ; Nakata, K. ; Aruga, J. ; Mikoshiba, K. / Zic3 is involved in the left-right specification of the Xenopus embryo. In: Development. 2000 ; Vol. 127, No. 22. pp. 4787-4795.
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AB - Establishment of left-right (L-R) asymmetry is fundamental to vertebrate development. Several genes involved in L-R asymmetry have been described. In the Xenopus embryo, Vg1/activin signals are implicated upstream of asymmetric nodal related 1 (Xnr1) and Pitx2 expression in L-R patterning. We report here that Zic3 carries the left-sided signal from the initial activin-like signal to determinative factors such as Pitx2. Overexpression of Zic3 on the right side of the embryo altered the orientation of heart and gut looping, concomitant with disturbed laterality of expression of Xnr1 and Pitx2, both of which are normally expressed in the left lateral plate mesoderm. The results indicate that Zic3 participates in the left-sided signaling upstream of Xnr1 and Pitx2. At early gastrula, Zic3 was expressed not only in presumptive neuroectoderm but also in mesoderm. Correspondingly, overexpression of Zic3 was effective in the L-R specification at the early gastrula stage, as revealed by a hormone-inducible Zic3 construct. The Zic3 expression in the mesoderm is induced by activin β or Vg1, which are also involved in the left-sided signal in L-R specification. These findings suggest that an activin-like signal is a potent upstream activator of Zic3 that establishes the L-R axis. Furthermore, overexpression of the zinc-finger domain of Zic3 on the right side is sufficient to disturb the L-R axis, while overexpression of the N-terminal domain on the left side affects the laterality. These results suggest that Zic3 has at least two functionally important domains that play different roles and provide a molecular basis for human heterotaxy, which is an L-R pattern anomaly caused by a mutation in human ZIC3.

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