Pax genes and their roles in cell differentiation and development

Mansouri, Ahmed; Hallonet, Marc; Gruß, Peter

doi:10.1016/s0955-0674(96)80087-1

Cited by 295 publications

(237 citation statements)

References 74 publications

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“…The family encodes a series of highly conserved DNAbinding proteins, whose expression is tissue-speci®c and which play an important role in the development of many organs during embryogenesis (Dahl et al, 1997;Mansouri et al, 1996). To date, nine members of this family have been identi®ed in mice and human, designated PAX1 through PAX9 (reviewed in SchaÈ fer, 1998).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR

et al. 2000

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The aberrant expression of the transcription factors PAX3 and PAX3/FKHR associated with rhabdomyosarcoma (RMS), solid tumors displaying muscle cell features, suggests that these proteins play an important role in the pathogenesis of RMS. We could previously demonstrate that one of the oncogenic functions of PAX3 and PAX3/FKHR in RMS is protection from apoptosis. BCL-XL is a prominent anti-apoptotic protein present in normal skeletal muscle and RMS cells. In the present study, we establish that BCL-XL is transcriptionally modulated by PAX3 and PAX3/FKHR, since enhanced expression of both PAX proteins stimulates transcription of endogenous BCL-XL mRNA in a cell type speci®c manner. Further, we present evidence that both PAX3 and PAX3/FKHR can transcriptionally activate the Bcl-x gene promoter in cotransfection assays. Using electrophoretic mobility shift assays, an ATTA binding site for PAX3 and PAX3/FKHR could be localized in the upstream promoter region (position 742 to 739). Finally, ectopic overexpression of either PAX3, PAX3/FKHR or BCL-XL can rescue tumor cells from apoptosis induced by antisense treatment. These results suggest that at least part of the anti-apoptotic e ect of PAX3 and PAX3/FKHR is mediated through direct transcriptional modulation of the prominent antiapoptotic protein BCL-XL.

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Section: Introductionmentioning

confidence: 99%

Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR

et al. 2000

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“…These transcription factors are expressed in an orderly manner during fetal development. 1,2 They have a critical role in the formation of tissues and organs during embryonic development and are also crucial for maintaining the normal function of certain cells after birth. 1,2 As a transcription factor, PAX 8 is known to control the development of the central nervous system, eye, kidney, thyroid gland, organs deriving from the mesonephric (wolffian) duct, and those related to the Mü llerian duct.…”

mentioning

confidence: 99%

“…1,2 They have a critical role in the formation of tissues and organs during embryonic development and are also crucial for maintaining the normal function of certain cells after birth. 1,2 As a transcription factor, PAX 8 is known to control the development of the central nervous system, eye, kidney, thyroid gland, organs deriving from the mesonephric (wolffian) duct, and those related to the Mü llerian duct. [3][4][5][6][7][8][9] Transcription factors are identified in the nuclei of cell types that are under their developmental control during organogenesis, but they often disappear in mature tissues.…”

mentioning

confidence: 99%

“…[3][4][5][6][7][8][9] Transcription factors are identified in the nuclei of cell types that are under their developmental control during organogenesis, but they often disappear in mature tissues. 1,2 However, these transcription factors may re-express in an organ-specific manner during neoplastic transformation. 10 For example, PAX 8 is abundantly expressed by renal blastema cells during nephrogenesis, and then is noted in only a few renal parenchymal cells in the mature kidney, but is identified again in renal cell carcinoma.…”

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confidence: 99%

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PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study

et al. 2011

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PAX 8 is a transcription factor that is essential for embryonic development of the kidney, Mü llerian organs, and thyroid. It may also have a role in tumor development in these organs. The diagnostic utility of PAX 8 has not been comprehensively studied. Formalin-fixed, paraffin-embedded tissue samples for non-neoplastic tissues (n ¼ 1601), primary neoplasms (n ¼ 933), and metastatic neoplasms (n ¼ 496) were subjected to PAX 8 immunostain. In non-neoplastic tissues, PAX 8 was consistently noted in glomerular parietal epithelial cells, renal collecting ductal cells, atrophic renal tubular epithelial cells regardless of nephronic segments, and epithelial cells of the endocervix, endometrium, fallopian tube, seminal vesicle, epidydimis, thyroid, pancreatic islet cells, and lymphoid cells. PAX 8 was not seen in the rest of the tissue samples. In primary neoplasms, PAX 8 was expressed by 194 of 240 (89%) renal cell neoplasms, by 238 of 267 (89%) Mü llerian-type neoplasms, by 65 of 65 (100%) thyroid follicular cell neoplasms, by 8 of 8 (100%) nephrogenic adenomas, and by 17 of 17 (100%) lymphomas. Weak focal staining was noted in 5 of 12 (42%) cases of parathyroid hyperplasia/adenoma and in 6 of 17 (35%) well-differentiated neuroendocrine tumors of the pancreas. PAX 8 was not seen in other neoplasms. In metastatic neoplasms, PAX 8 was expressed by 90 of 102 (88%) metastatic renal cell carcinomas, by 57 of 63 metastatic Mü llerian tumors (90%), and by 6 of 6 metastatic papillary thyroid carcinomas (100%). There was also weak focal staining for 1 of 15 metastatic small cell carcinomas and for 1 of 9 metastatic well-differentiated neuroendocrine carcinomas. PAX 8 was not seen in other metastatic neoplasms. It can be successfully identified in routinely processed tissue samples, and its expression is mostly nuclear. PAX 8 expression in nonneoplastic mature tissues is limited to the organs, the embryonic development of which depends on this transcription factor. This tissue/cell-specific expression is maintained during both neoplastic transformation and metastasis. PAX 8 is a sensitive and specific marker for tumors of renal, Mü llerian, or thyroid origin in both primary and metastatic sites.

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“…Pax genes are found in a wide variety of organisms including the placozoans, cnidarians, insects, mollusks, tunicates, and vertebrates (Vorobyov and Horst, 2006). In vertebrates there are nine Pax genes, which can be split into different classes based on sequence homology and presumed ancestral relationships (Mansouri et al, 1996;Stuart and Gruss, 1996;Vorobyov and Horst, 2006). Pax2 groups with Pax5 and Pax8, and in many regions of the embryo either two or all three of the Pax2/5/8 sub-family, are co-regulated (Krelova et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Pax2 modulates proliferation during specification of the otic and epibranchial placodes

Freter¹,

Muta²,

O’Neill³

et al. 2012

Developmental Dynamics

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Background: The inner ear and epibranchial ganglia of vertebrates arise from a shared progenitor domain that is induced by FGF signalling, the posterior placodal area (PPA), before being segregated by Wnt signalling. One of the first genes activated in the PPA is the transcription factor Pax2. Loss-of-and gain-of function studies have defined a role for Pax2 in placodal morphogenesis and later inner ear development, but have not addressed the role Pax2 plays during the formation and maintenance of the PPA. Results: To understand the role of Pax2 during the development of the PPA, we used over-expression and repression of Pax2. Both gave rise to a smaller otocyst and repressed the formation of epibranchial placodes. In addition, cell cycle analysis revealed that Pax2 suppression reduced proliferation of the PPA. Key FindingsNeither suppression nor over-expression of Pax2 affects the extent of the precursor region of the inner ear and epibranchial placodes, the PPA. Suppressing and over-expressing Pax2 does affect the differentiation of the inner ear and the epibranchial placodes. Pax2 suppression reduces proliferation of PPA precursors.

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Pax genes and their roles in cell differentiation and development

Cited by 295 publications

References 74 publications

Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR

Transcriptional modulation of the anti-apoptotic protein BCL-XL by the paired box transcription factors PAX3 and PAX3/FKHR

PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study

Pax2 modulates proliferation during specification of the otic and epibranchial placodes

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