Perplexing Pax: From puzzle to paradigm

School of Exercise Biomedical and Health Science, Edith Cowan University, Joondalup, Western Australia.
Developmental Dynamics (Impact Factor: 2.38). 10/2008; 237(10):2791-803. DOI: 10.1002/dvdy.21711
Source: PubMed


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 · 3.54 Impact Factor
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    • "The most significant finding is a population of cells that co-express Pax3, Sox2 and p75Ngfr have been identified. These proteins are commonly expressed in multipotent cells in a variety of tissues [32]–[35] and while the role of Pax3 in Schwann cells remains largely undetermined, its overarching role in other tissues is maintenance of progenitor cells across the life span [9]. In Schwann cells, Sox2 has been shown to increase responsiveness to proliferative stimuli, prevent myelin gene expression and inhibit differentiation [27], [36]. "
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    ABSTRACT: Pax3 has numerous integral functions in embryonic tissue morphogenesis and knowledge of its complex function in cells of adult tissue continues to unfold. Across a variety of adult tissue lineages, the role of Pax3 is principally linked to maintenance of the tissue's resident stem/progenitor cell population. In adult peripheral nerves, Pax3 is reported to be expressed in nonmyelinating Schwann cells, however, little is known about the purpose of this expression. Based on the evidence of the role of Pax3 in other adult tissue stem and progenitor cells, it was hypothesised that the cells in adult peripheral nerve that express Pax3 may be peripheral glioblasts. Here, methods have been developed for identification and visualisation of Pax3 expressant cells in normal 60 day old mouse peripheral nerve that allowed morphological and phenotypic distinctions to be made between Pax3 expressing cells and other nonmyelinating Schwann cells. The distinctions described provide compelling support for a resident glioblast population in adult mouse peripheral nerve.
    PLoS ONE 03/2013; 8(3):e59184. DOI:10.1371/journal.pone.0059184 · 3.23 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 11/2012; 241(11):1716-28. DOI:10.1002/dvdy.23856 · 2.38 Impact Factor
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