Expression pattern of Irx1 and Irx2 during mouse digit development

Zülch, Armin; Becker, May-Britt; Gruß, Peter

doi:10.1016/s0925-4773(01)00411-7

Cited by 32 publications

(30 citation statements)

References 7 publications

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“…As reported previously, Irx1 and Irx2 are expressed in the metatarsal cartilage and the cartilage of the phalanges around E13.5 (31) (Fig. 4A, B, D, and E).…”

Section: Fig 3 Mhb Integrity In Irx2supporting

confidence: 86%

The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

Lebel

Agarwal

Cheng

et al. 2003

Molecular and Cellular Biology

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The Iroquois homeobox (Irx) genes have been implicated in the specification and patterning of several organs in Drosophila and several vertebrate species. Misexpression studies of chick, Xenopus, and zebra fish embryos have demonstrated that Irx genes are involved in the specification of the midbrain-hindbrain boundary. All six murine Irx genes are expressed in the developing heart, suggesting that they might possess distinct functions during heart development, and a role for Irx4 in normal heart development has been recently demonstrated by gene-targeting experiments. Here we describe the generation and phenotypic analysis of an Irx2-deficient mouse strain. By targeted insertion of a lacZ reporter gene into the Irx2 locus, we show that lacZ expression reproduces most of the endogenous Irx2 expression pattern. Despite the dynamic expression of Irx2 in the developing heart, nervous system, and other organs, Irx2-deficient mice are viable, are fertile, and appear to be normal. Although chick Irx2 has been implicated in the development of the midbrain-hindbrain region, we show that Irx2-deficient mice develop a normal midbrain-hindbrain boundary. Furthermore, Irx2-deficient mice have normal cardiac morphology and function. Functional compensation by other Irx genes might account for the absence of a phenotype in Irx2-deficient mice. Further studies of mutant mice of other Irx genes as well as compound mutant mice will be necessary to uncover the functional roles of these evolutionarily conserved transcriptional regulators in development and disease.The Drosophila Iroquois complex (Iro-C) was first identified as prepattern genes that control the patterning of notum bristles (see reference 15 for a review). Iro-C contains three highly related homeobox genes (araucan [ara], caupolican [caup], and mirror [mir]), which encode transcriptional regulators that control the expression of the proneural genes, such as achaete and scute. These Iroquois homeobox (Irx) genes also play regulatory roles in the development of other structures, including the head, eye, and wing veins.The structure and organization of vertebrate Irx genes are evolutionarily conserved (15). For example, in mouse and human, six Irx genes (Irx1 to Irx6) are found in two clusters; Iro-A contains Irx1, Irx2, and Irx4, Irx5, and Irx6 (26). Similar to their Drosophila counterparts, the vertebrate Irx genes also possess regulatory functions in the specification and patterning of early embryos and several organs. Misexpression studies have revealed the roles of three Xenopus Irx genes (Xiro1, -2, and -3) in the regulation of vertebrate proneural genes and the specification of the neural plate (3, 16). After the neural plate is specified, the Irx genes are also involved in the anteroposterior and dorsoventral patterning of the neural tube. In chicken embryos, Irx3 is implicated in determining the positioning of zona limitans intrathalamica at the border between the diencephalon and telencephalon (21) as well as in the dorsoventral patterning of the spinal cord...

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“…As reported previously, Irx1 and Irx2 are expressed in the metatarsal cartilage and the cartilage of the phalanges around E13.5 (31) (Fig. 4A, B, D, and E).…”

Section: Fig 3 Mhb Integrity In Irx2supporting

confidence: 86%

The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

Lebel

Agarwal

Cheng

et al. 2003

Molecular and Cellular Biology

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“…The Iroquois transcription factor family, which plays multiple roles in many metazoan developmental processes (5,8), has recently been shown to be involved in the development of many cancers (6,(38)(39)(40)(41). For example, IRX3 downregulation in breast of depression, liver disease, and osteoarthritis (60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, IRX1 was identified as a potential tumor-suppressor gene in head and neck squamous cell carcinoma (HNSCC) and gastric cancer (6,7); however, further efforts are required to determine the exact function of IRX1 in the development of other cancers, including osteosarcoma. IRX1 is involved in limb development (8) and the etiology of kyphoscoliosis (9), suggesting that aberrant IRX1 expression may contribute to abnormal bone formation. Moreover, a gain of chromosome 5p15.33 (chromosomal location of IRX1) has been frequently detected in osteosarcoma cell lines (10).…”

Section: Introductionmentioning

confidence: 99%

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

Lu¹,

Song²,

Tang³

et al. 2015

J. Clin. Invest.

111

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“…Specifically, zebrafish Irx1b, which is highly homologous to mouse Irx1, is expressed in the trabeculae of the ventricle as well as in the compact working myocardium, and knockdown of Irx1b results in slower heart rates via a mechanism that has not been studied. 19 Since recent studies show that Irx1 has been implicated in other organ development and cancer, [51][52][53][54] it would be of interest to examine the effects of Irx1 knockout (KO) in mouse hearts.…”

Section: Irx1 and Irx2mentioning

confidence: 99%

Iroquois Homeodomain Transcription Factors in Heart Development and Function

Kim

Rosén²,

Bruneau³

et al. 2012

Circulation Research

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Numerous cardiac transcription factors play overlapping roles in both the specification and proliferation of the cardiac tissues and chambers during heart development. It has become increasingly apparent that cardiac transcription factors also play critical roles in the regulation of expression of many functional genes in the prenatal and postnatal hearts. Accordingly, mutations of cardiac transcription factors cannot only result in congenital heart defects but also alter heart function thereby predisposing to heart disease and cardiac arrhythmias. In this review, we summarize the roles of Iroquois homeobox (Irx) family of transcription factors in heart development and function. In all, 6 Irx genes are expressed with distinct and overlapping patterns in the mammalian heart. Studies in several animal models demonstrate that Irx genes are important for the establishment of ventricular chamber properties, the ventricular conduction system, as well as heterogeneity of the ventricular repolarization Key Words: Iroquois homeobox Ⅲ cardiac transcription factor Ⅲ cardiac development T he heart is the first functional organ formed in the mammalian embryo in order to provide the necessary nutrients for growth and development. 1 Throughout life, the contraction sequence of the heart in each beat is orchestrated by well-defined electric activation patterns designed to enable efficient mechanical pumping of blood. Electric impulses begin in the auto-rhythmic cells of the sinoatrial node and propagate to the atria, thereby initiating contraction and blood propulsion into the relaxed and compliant ventricles. The electric impulses then proceed with highly controlled delay to the ventricles via the specialized ventricular conduction system (VCS), comprising sequentially the atrioventricular node, His bundles, left and right bundle branches, and Purkinje fiber network. Electrical stimulation of the VCS ultimately results in highly ordered ventricular contractions proceeding from the apex toward the base as well as from the endomyocardium to epimyocardium, 2,3 thus enabling efficient blood ejection into the systemic and pulmonary circulations. The ventricles then repolarize and relax in reverse order from epimyocardium to endomyocardium and from the base toward the apex.Efficient heart function requires the precise and harmonious union of structure and function, which is achieved by precisely controlled patterns of gene expression within different cardiac regions at developmental stages. For example, in the early embryo, cardiac transcription factors (TFs) such as Nkx2-5, 4 Gata, 5 Hand, 6 Nfat, 7 and the T-box family members 8 regulate many key aspects of heart development, including cardiac chamber septation, valve formation, and outflow tract morphogenesis. Consequently, mutations in these TFs are directly associated with several congenital heart diseases. 9 On the other hand, some of these same genes control expression of key functional genes regulating contractile and electric properties of the mature heart. 10 -13...

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Expression pattern of Irx1 and Irx2 during mouse digit development

Cited by 32 publications

References 7 publications

The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

Iroquois Homeodomain Transcription Factors in Heart Development and Function

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