Pax2 modulates proliferation during specification of the otic and epibranchial placodes

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. 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.

Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage

“…Nevertheless, neurod expression within the otic vesicle, which is confined to an anterior-ventral position in wild-type embryos, is present throughout the remaining epithelial ball in b380 mutants, showing that all otic cells adopt a neuronal fate in this genotype. Cell death as well as proliferation might also play an important role for proper neuronal progenitor formation, because Pax2 has been shown to play an important role in proliferation in the OEPD (Freter et al, 2012).…”

“…Studies in various species have shown that OEPD formation is triggered by Fibroblast growth factor (Fgf) ligands secreted by the hindbrain and subjacent mesendoderm (Phillips et al, 2001;Léger and Brand, 2002;Maroon et al, 2002;Alvarez et al, 2003;Wright and Mansour, 2003;Ladher et al, 2005). In response to these signals, cells express Pax8 and Pax2, two members of the Pax2/5/8 transcription factor family, which are crucial regulators of OEPD formation and proper inner ear development (Brand et al, 1996;Pfeffer et al, 1998;Hans et al, 2004;Mackereth et al, 2005;Bouchard et al, 2010;Freter et al, 2012). The subsequent segregation of otic and epibranchial progenitors is mediated by Wnt signaling in a Pax2-dependent manner (Freter et al, 2008;McCarroll et al, 2012).…”

A systems-level approach reveals new gene regulatory modules in the developing ear

“…Although these and previous data implicate Pax2 as a key factor for otic specification and proliferation in chick (Christophorou et al, 2010; Freter et al, 2012), the mouse otic placode still forms in the absence of Pax2 (Burton et al, 2004; Favor et al, 1996; Torres et al, 1996) or Pax2 and Pax8 function (Bouchard et al, 2010). The fact that sauropsids have lost the Pax8 gene (Christophorou et al, 2010; Freter et al, 2012) could explain the more prominent role of Pax2 in the otic GRN.…”

“…1A; Ladher et al, 2000; Maroon et al, 2002; Martin and Groves, 2006; Nechiporuk et al, 2007; Nikaido et al, 2007; Phillips et al, 2001; Sun et al, 2007; Urness et al, 2010; Wright and Mansour, 2003). The OEP state is characterized by transcription factors like Foxi1/3 (Khatri et al, 2014; Ohyama and Groves, 2004; Solomon et al, 2003), Dlx genes (Brown et al, 2005; Solomon and Fritz, 2002), Pax2/8 (Christophorou et al, 2010; Freter et al, 2012; Hans et al, 2004; Mackereth et al, 2005) and Spalt4 (Barembaum and Bronner-Fraser, 2007, 2010; Schlosser, 2006). After this step, Wnt and Notch pathways cooperate to promote otic and repress epibranchial character (Fig.…”

Early formation of the Müllerian duct is regulated by sequential actions of BMP/Pax2 and FGF/Lim1 signaling

“…To describe molecular and cellular events during early MD development, we examined expression patterns of Pax2, Lim1 and N-cadherin (also known as cadherin 2) in the CE adjacent to the WD, the region known to form MD, in HH16-24 embryos. We excluded Pax8, an early MD marker observed in mice because avian species lost the Pax8 gene during their evolution (Freter et al, 2012). As shown in Fig.…”