The molecular basis of craniofacial placode development

Abstract

The sensory organs of the vertebrate head originate from simple ectodermal structures known as cranial placodes. All cranial placodes derive from a common domain adjacent to the neural plate, the pre-placodal region, which is induced at the border of neural and non-neural ectoderm during gastrulation. Induction and specification of the pre-placodal region is regulated by the FGF, BMP, WNT and retinoic acid signaling pathways, and characterized by expression of the EYA and SIX family of transcriptional regulators. Once the pre-placodal region is specified, different combinations of local signaling molecules and placode-specific transcription factors, including competence factors, promote the induction of individual cranial placodes along the neural axis of the head region. In this review, we summarize the steps of cranial placode development and discuss the roles of the main signaling molecules and transcription factors which regulate these steps during placode induction, specification and development.

Gene, cell, and organ multiplication drives inner ear evolution

“…Interestingly enough, several other transcription factors that are essential for vertebrate ear development, such as Eya1/Six1 (Xu et al, 1999; Zou et al, 2008), Gata3 (Duncan and Fritzsch, 2013; Karis et al, 2001) are also essential for both kidney and ear development. In addition, several other transcription factors are needed for ear development (Foxi3, Fgf3/10, Fgfr2, Sox9, Tfap2a (Alsina and Streit, 2016; Birol et al, 2016; Khatri et al, 2014; McMahon, 2016; Papadopoulos et al, 2016; Singh and Groves, 2016). Based on the evolution of statocysts in diploblasts, one could argue that evolution of the proneural gene regulatory network (GRN), involving possibly Eya1/Six1, Foxi3, Pax2/8 and Gata3 network of interacting factors and its dependence on Fgfr2 signaling (Pauley et al, 2003; Pirvola et al, 2000), evolved in ectodermal sensory placodes and was co-opted for mesodermal kidney development in triploblasts.…”

“…Kidney development also depends on Fgf 7/10 ligands signaling mostly via the Fgfr1 receptor (Bates, 2007; Rossini et al, 2005), but also Fgfr2 (McMahon, 2016). BMP4 downregulation combined with Fgf expression is an essential early step in neural induction (Fritzsch et al, 2006a; Meinhardt, 2015) that results in an unclear proportion of BMP4/Fgf signaling (Singh and Groves, 2016). This essential step of Bmp4 suppression and Fgf expression is not only essential for placode induction but also suffices to induce stem cells into differentiation as ear organoids in culture (Liu et al, 2016).…”

“…How much of the developmental cascade of otic placode/otocyst development is recapitulated in these in vitro conditions and how closely the level of BMP4/Fgf protein signaling needs to be regulated for this development to occur remains to be determined. During neuronal development (most likely including the ear), the expression of early transcription factors leads to the expression of pro-proliferative and neural-fate stabilizing transcription factors, such as Otx2, Gbx2, Geminin , and Sox2 (Janesick et al, 2013; Singh and Groves, 2016; Yellajoshyula et al, 2011) and the Baf complex (Seo et al, 2005a; Seo et al, 2005b), that ultimately regulates chromatin remodeling and proneural bHLH gene expression. Level of bHLH gene expression in turn depends on the action of the Baf complex variably supported by Eya1/Six1, Pax2/8, Sox2, Foxi3 and Gata3.…”

“…How all of these early transcription factors interact to define the level and topology of bHLH gene activation and how Wnt signaling fits in to regulate the size of the otic placode (Ohyama et al, 2007) remains to be determined experimentally. Loss of several factors can result in either incomplete invagination of the otic placode in mice mutant for Gata3 (Karis et al, 2001) or Pax2/8 (Bouchard et al, 2010), complete suppression of ear placode invagination such as in Foxi3 mutants (Birol et al, 2016; Singh and Groves, 2016) or in frogs exposed to RA (Fritzsch et al, 1998) or even incomplete formation of the ear following loss of Fgfr2 (Pirvola et al, 2000), indicating that several interactions are needed to move an otic placode forward to form an otocyst.…”

“…Pax2/8 as well as Foxi1/3 are chromatin remodeling factors that could enable expression of many other genes (Sharma et al, 2015; Singh and Groves, 2016). While these transcription factors can already be assembled into a rudimentary GRN for early neurosensory fate determination in developing otic region (Riddiford and Schlosser, 2016) and as initial aspects or otic placode enhancers begin to surface (Chen and Streit, 2015), the details of this network require more work to ensure guidance of otic development out of stem cells.…”