The int-2 proto-oncogene is responsible for induction of the inner ear

Represa, Juan; León, Yolanda; Miner, Cristina; Giráldez, Fernando

doi:10.1038/353561a0

Cited by 172 publications

(104 citation statements)

References 14 publications

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“…However, little is known to date about the molecular basis underlying these inductive and determinative processes during development of the inner ear. Embryological and genetic studies have revealed important roles for FGF-3 during induction and/or compartimentalization of the inner ear (Represa et al, 1991;Mansour et al, 1993). FGF-3 is expressed in the hindbrain and otic vesicle during its patterning and differentiation (Wilkinson et al, 1989) and also FGF-2 is expressed by the otic vesicle (Dono and Zeller, unpublished data).…”

Section: Discussion Ld Proteins and Establishment Of The Vestibular Amentioning

confidence: 99%

Limb deformity proteins during avian neurulation and sense organ development

Pompa

James

Zeller

1995

Developmental Dynamics

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The nuclear Limb deformity (Ld) proteins (formins) are expressed during the avian primitive streak stages. Initially, they are detected predominantly in cells of the forming notochord, scattered mesodermal precursors and the induced neural plate. No expression is detected in endodermal cells. The subsequent graded distribution of Ld positive cells along the anterior-posterior axis of the neural tube follows the antero-posterior progression of its differentiation. The Ld proteins are also differentially expressed during induction and development of both the inner ear and eye. An unequal distribution of Ld proteins along the dorso-ventral axis of the otic vesicle is observed during its initial patterning. In the eye, the Ld proteins are expressed by the optic vesicle during secondary induction of the lens placode. Following induction, the proteins are also expressed by the newly formed lens placode, a process which is reminiscent of homeogenetic induction. During differentiation of the retina and lens, the Ld domains seem to demarcate territories, giving rise to specific eye structures. A comparative analysis of the Ld distribution and BrdU incorporation in the two sense organs indicates that the proteins are predominantly expressed by committed and/or differentiating (post-mitotic) cells. In general, expression of Ld proteins is induced during determination and remains during differentiation of particular celltypes. This study implies that the nuclear Ld proteins are involved in morphogenesis of both neuro-ectodermal and mesodermal structures.

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Section: Discussion Ld Proteins and Establishment Of The Vestibular Amentioning

confidence: 99%

Limb deformity proteins during avian neurulation and sense organ development

Pompa

James

Zeller

1995

Developmental Dynamics

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“…It has become clear that FGF-derived signals constitute a significant part of this inductive capacity (Represa et al, 1991;Ladher et al, 2000;Vendrell et al, 2000;Phillips et al, 2001;Leger and Brand, 2002;Maroon et al, 2002;Liu et al, 2003). In zebrafish, fgf3/8 are expressed in mesendoderm and hindbrain and appear to function as inductive signals at multiple points during otic placode development Phillips et al, 2001;Leger and Brand, 2002;Maroon et al, 2002;Liu et al, 2003).…”

Section: Requirement For Foxi1 In Fgf3/8 Induction Of the Otic Placodementioning

confidence: 99%

“…Fibroblast growth factor (FGF) molecules have been identified as inductive signals for otic placode development in several vertebrate species (Represa et al, 1991;Mansour et al, 1993;De Moerlooze et al, 2000;Ohuchi et al, 2000;Pirvola et al, 2000Pirvola et al, , 2002Vendrell et al, 2000;Phillips et al, 2001;Leger and Brand, 2002;Maroon et al, 2002). Depletion of FGF3 prevents otic vesicle formation in tissue explants from chick (Represa et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Genetic interactions underlying otic placode induction and formation

Solomon

Kwak

Fritz

2004

Developmental Dynamics

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The formation of the otic placode is a complex process requiring multiple inductive signals. In zebrafish, fgf3 and fgf8, dlx3b and dlx4b, and foxi1 have been identified as the earliest-acting genes in this process. fgf3 and fgf8 are required as inductive signals, whereas dlx3b, dlx4b, and foxi1 appear to act directly within otic primordia. We have investigated potential interactions among these genes. Depletion of either dlx3b and dlx4b or foxi1 leads to a delay of pax2a expression in the otic primordia and reduction of the otic vesicle. Depletion of both foxi1 and dlx3b results in a complete ablation of otic placode formation. A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8, and a weaker interaction among dlx3b, fgf3, and fgf8. Misexpression of foxi1 can induce expression of pax8, an early marker for the otic primordia, in embryos treated with an inhibitor of fibroblast growth factor (FGF) signaling. Conversely, morpholino knockdown of foxi1 blocks ectopic pax8 expression and otic vesicle formation induced by misexpression of fgf3 and/or fgf8. The observed genetic interactions suggest a model in which foxi1 and dlx3b/dlx4b act in independent pathways together with distinct phases of FGF signaling to promote otic placode induction and development. Developmental Dynamics 230:419 -433, 2004.

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“…This may be caused by the lack of antigen preservation, by nonspecific staining reaction, or by other mechanisms not fully understood, leading to negative immunohistochemical staining result. In the mouse, fgf4 and int2 are known to be expressed during embryogenesis (22,23). Assuming the expression pattern to be similar in humans, no expression would be expected in normal adult tissues.…”

Section: Discussionmentioning

confidence: 99%

FGF4 and INT2 Oncogenes Are Amplified and Expressed in Kaposi's Sarcoma

et al. 2000

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Kaposi's sarcoma (KS) is a vascular tumor, the pathogenesis of which has been suggested to include human herpesvirus 8 (HHV-8) as well as various cytokines and growth factors. Very little is known about cytogenetic and molecular genetic changes in KS. We studied DNA copy number changes in KS and found a recurrent gain at 11q13. We then analyzed the amplification and expression status of two known oncogenes, FGF4 and INT2, residing at 11q13. Comparative genomic hybridization, interphase fluorescence in situ hybridization with yeast artificial chromosome probes containing FGF4 and INT2, and immunoperoxidase immunostaining with anti-FGF4 and -INT2 antibodies were used on 12 KS samples. All samples tested were shown by polymerase chain reaction to be HHV-8 positive. A recurrent gain at 11q13 was shown by comparative genomic hybridization in 4 of 10 cases studied. Of six cases studied by interphase fluorescence in situ hybridization, four showed a 3-to 4-fold amplification with the probes containing FGF4 and INT2. Expression of FGF4 and INT2 was found in nine and three cases, respectively, of nine studied. Amplification and expression of these genes is particularly interesting in the context of oncovirus involvement, because INT2 is a homolog of mouse int2, which causes mammary carcinoma in mice when activated by integration of retrovirus mouse mammary tumor virus. This raises the question of whether HHV-8 represents an integrating oncovirus that causes amplification and activation of genomic oncogenes in humans.

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The int-2 proto-oncogene is responsible for induction of the inner ear

Cited by 172 publications

References 14 publications

Limb deformity proteins during avian neurulation and sense organ development

Limb deformity proteins during avian neurulation and sense organ development

Genetic interactions underlying otic placode induction and formation

FGF4 and INT2 Oncogenes Are Amplified and Expressed in Kaposi's Sarcoma

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