Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism

Kunio Kitamura, Hirohito Miura, Sachiko Miyagawa-Tomita, Masako Yanazawa, Yuko Katoh-Fukui, Rika Suzuki, Hideyo Ohuchi, Atuko Suehiro, Yoshiko Motegi, Yoko Nakahara, Shunzo Kondo, Minesuke Yokoyama

Research output: Contribution to journalArticle

353 Citations (Scopus)

Abstract

Pitx2, a bicoid-related homeobox gene, is involved in Rieger's syndrome and the left-right (L-R) asymmetrical pattern formation in body plan. In order to define the genomic structure and roles of Pitx2, we analyzed the genomic structure and generated Pitx2-deficient mice with the lacZ gene in the homeobox-containing exon of Pitx2. We were able to show that among three isoforms of Pitx2, Pitx2c shows asymmetrical expression whereas Pitx2a, Pitx2b and Pitx2c show symmetrical expression. In Pitx2(-/-) embryos there was an increase in mesodermal cells in the distal end of the left lateral body wall and an amnion continuous with the lateral body wall thickened in its mesodermal layer. These changes resulted in a failure of ventral body wall closure. In lung and heart in which Pitx2 is expressed asymmetrically, right pulmonary isomerism, atrioventricular canals with prominent swelling, and juxtaposition of the atrium were detected. The hearts failed to develop tricuspid and mitral valves and a common atrioventricular valve forms. Further, dysgenesis of the Pitx2(-/-) extraocular muscle and thickening of the mesothelial layer of cornea were observed in the ocular system where Pitx2 is expressed symmetrically, and these resulted in enophthalmos. The present study shows that Pitx2 expressed in various sites participates in morphogenesis through three types of actions: the involvement of asymmetric Pitx2 expression in the entire morphogenetic process of L-R asymmetric organs; the involvement of asymmetric Pitx2 expression in the regional morphogenesis of asymmetric organs; and finally the involvement of symmetric Pitx2 expression in the regional morphogenesis of symmetric organs.

Original languageEnglish
Pages (from-to)5749-5758
Number of pages10
JournalDevelopment
Volume126
Issue number24
Publication statusPublished - Dec 1999
Externally publishedYes

Fingerprint

Isomerism
Mesoderm
Morphogenesis
Homeobox Genes
Lung
Oculomotor Muscles
Body Patterning
Enophthalmos
Amnion
Lac Operon
Tricuspid Valve
Mitral Valve
Cornea
Exons
Protein Isoforms
Embryonic Structures

Keywords

  • Gene targeting
  • Isoforms
  • Mouse
  • Pitx2
  • Rieger's syndrome
  • Symmetric/asymmetric expression

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Kitamura, K., Miura, H., Miyagawa-Tomita, S., Yanazawa, M., Katoh-Fukui, Y., Suzuki, R., ... Yokoyama, M. (1999). Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. Development, 126(24), 5749-5758.

Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. / Kitamura, Kunio; Miura, Hirohito; Miyagawa-Tomita, Sachiko; Yanazawa, Masako; Katoh-Fukui, Yuko; Suzuki, Rika; Ohuchi, Hideyo; Suehiro, Atuko; Motegi, Yoshiko; Nakahara, Yoko; Kondo, Shunzo; Yokoyama, Minesuke.

In: Development, Vol. 126, No. 24, 12.1999, p. 5749-5758.

Research output: Contribution to journalArticle

Kitamura, K, Miura, H, Miyagawa-Tomita, S, Yanazawa, M, Katoh-Fukui, Y, Suzuki, R, Ohuchi, H, Suehiro, A, Motegi, Y, Nakahara, Y, Kondo, S & Yokoyama, M 1999, 'Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism', Development, vol. 126, no. 24, pp. 5749-5758.
Kitamura K, Miura H, Miyagawa-Tomita S, Yanazawa M, Katoh-Fukui Y, Suzuki R et al. Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. Development. 1999 Dec;126(24):5749-5758.
Kitamura, Kunio ; Miura, Hirohito ; Miyagawa-Tomita, Sachiko ; Yanazawa, Masako ; Katoh-Fukui, Yuko ; Suzuki, Rika ; Ohuchi, Hideyo ; Suehiro, Atuko ; Motegi, Yoshiko ; Nakahara, Yoko ; Kondo, Shunzo ; Yokoyama, Minesuke. / Mouse Pitx2 deficiency leads to anomalies of the ventral body wall, heart, extra- and periocular mesoderm and right pulmonary isomerism. In: Development. 1999 ; Vol. 126, No. 24. pp. 5749-5758.
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