Article

Perplexing Pax: from puzzle to paradigm.

School of Exercise Biomedical and Health Science, Edith Cowan University, Joondalup, Western Australia.
Developmental Dynamics (Impact Factor: 2.67). 10/2008; 237(10):2791-803. DOI: 10.1002/dvdy.21711
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ABSTRACT Pax transcription factors are critical for the development of the central nervous system (CNS) where they have a biphasic role, initially dictating CNS regionalization, while later orchestrating differentiation of specific cell subtypes. While a plethora of expression, misexpression, and mutation studies lend support for this argument and clarify the importance of Pax genes in CNS development, less well understood, and more perplexing, is the continued Pax expression in the adult CNS. In this article we explore the mechanism of action of Pax genes in general, and while being cognizant of existing developmental data, we also draw evidence from (1) adult progenitor cells involved in regeneration and tissue maintenance, (2) specific expression patterns in fully differentiated adult cells, and (3) analysis of direct target genes functioning downstream of Pax proteins. From this, we present a more encompassing theory that Pax genes are key regulators of a cell's measured response to a dynamic environment.

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Available from: Melanie Ziman, Nov 06, 2014
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    • "Among the Pax genes, Pax6 and Pax7 are expressed in regionally restricted patterns in the developing brain and are involved in neuronal proliferation, brain regionalization, cell differentiation , and neuronal survival (Wehr and Gruss, 1996; Lang et al., 2007; Thompson et al., 2007; Osumi et al., 2008; Wang et al., 2008). Interestingly, Pax6 and Pax7 are also expressed in adult brains in restricted and well-localized cell groups and regions (Walther and Gruss, 1991; Stoykova and Gruss, 1994; Kawakami et al., 1997; Shin et al., 2003; Thompson and Ziman, 2011; Duan et al., 2012), suggesting their involvement in the maintenance of distinct neuronal identity (Ninkovic et al., 2010), in physiological functions in mature neurons (Stoykova and Gruss, 1994; Shin et al., 2003), and as key regulators of a cell's measured response to a dynamic environment (Blake et al., 2008). "
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    ABSTRACT: Many of the genes involved in brain patterning during development are highly conserved in vertebrates and similarities in their expression patterns help to recognize homologous cell types or brain regions. Among these genes, Pax6 and Pax7 are expressed in regionally restricted patterns in the brain and are essential for its development. In the present immunohistochemical study we analyzed the distribution of Pax6 and Pax7 cells in the brain of six representative species of tetrapods and lungfishes, the closest living relatives of tetrapods, at several developmental stages. The distribution patterns of these transcription factors were largely comparable across species. In all species only Pax6 was expressed in the telencephalon, including the olfactory bulbs, septum, striatum, and amygdaloid complex. In the diencephalon, Pax6 and Pax7 were distinct in the alar and basal parts, mainly in prosomeres 1 and 3. Pax7 specifically labeled cells in the optic tectum (superior colliculus) and Pax6, but not Pax7, cells were found in the tegmentum. Pax6 was found in most granule cells of the cerebellum and Pax7 labeling was detected in cells of the ventricular zone of the rostral alar plate and in migrated cells in the basal plate, including the griseum centrale and the interpeduncular nucleus. Caudally, Pax6 cells formed a column, whereas the ventricular zone of the alar plate expressed Pax7. Since the observed Pax6 and Pax7 expression patterns are largely conserved they can be used to identify subdivisions in the brain across vertebrates that are not clearly discernible with classical techniques.
    Frontiers in Neuroanatomy 08/2014; 8(75):1-20. DOI:10.3389/fnana.2014.00075 · 4.18 Impact Factor
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    • "Similarly, the expression of Pax2 and Pax8 is associated with proliferating progenitor populations in the developing kidney (Bouchard et al., 2002) and in the sensory patches of the inner ear (Li et al., 2004; Warchol and Richardson, 2009). Thus, the activity of Pax2 in the PPA is consistent with the generalized model of Pax function that has emerged (Blake et al., 2008). The question of how Pax2 maintains the PPA progenitor population is undoubtedly important and identification of interacting partners and downstream targets will illuminate these pathways. "
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    ABSTRACT: 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. Conclusions: Our results suggest that Pax2 functions in the maintenance but not the induction of the PPA. One role of Pax2 is to maintain proper cell cycle proliferation in the PPA. Developmental Dynamics 241:1716-1728, 2012. © 2012 Wiley Periodicals, Inc.
    Developmental Dynamics 11/2012; 241(11):1716-28. DOI:10.1002/dvdy.23856 · 2.67 Impact Factor
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    • "Wilms tumor suppressor gene 1 (WT1) was regarded as a useful marker in the diagnosis of ovarian serous carcinomas, which has been challenged by a diagnostic pitfall in effusion cytology, because mesothelial cells can demonstrate immunoreactivity for WT1[2]. PAX genes encode a family of nine well-characterized paired box transcription factors (PAX1–PAX9), which play important roles in embryogenesis and disease [3]. Recently, PAX8 was recommended "
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    ABSTRACT: OBJECTIVE: The aim of this study is to evaluate the detection of paired box gene 8 (PAX8) and p53 with immunohistochemistry in pelvic washing cell block sections. METHODS: A total of 92 cases were used in this study, which were assigned to three groups according to the cytopathology files. The first group with positive cytology including endometrial and ovarian carcinomas comprised 32 cases. The second group with suspicious cytology for endometrial or ovarian carcinomas consisted of 29 cases. The third group with negative cytology (regarded as mesothelial cells) included 31 cases. The pelvic washing cell blocks underwent immunohistochemistry to detect PAX8 and p53 expression. RESULTS: Immunoreactivity for PAX8 was found in 75% (24/32) of the cases in the group with positive cytology, in 6.9% (2/29) of the cases with suspicious cytology, and in none of the 31 cases with negative cytology (sensitivity: 75%; specificity: 100%; p<0.05). p53 expression was detected in 37.5% (12/32) of the cases in the first group, in 3.4% (1/29) of the cases in the second group, and in none of the cases in the third group (sensitivity: 37.5%; specificity: 100%; p<0.05). Moreover, the combined expression of PAX8 and p53 showed the same result as the single expression of p53 in the three groups. CONCLUSION: The detection of PAX8 and p53 is beneficial in recognizing metastatic carcinomas in pelvic washings, especially in cases with suspicious cytology, which additionally supports the Müllerian origin of these carcinomas.
    Gynecologic Oncology 08/2012; 127(3). DOI:10.1016/j.ygyno.2012.08.028 · 3.69 Impact Factor