Spalt4mediates invagination and otic placode gene expression in cranial ectoderm

Abstract

Vertebrate placodes are regions of thickened head ectoderm that contribute to paired sensory organs and cranial ganglia. We demonstrate that the transcription factor Spalt4 (also known as Sall4) is broadly expressed in chick preplacodal epiblast and later resolves to otic, lens and olfactory placodes. Ectopic expression of Spalt4 by electroporation is sufficient to induce invagination of non-placodal head ectoderm and prevent neurogenic placodes from contributing to cranial ganglia. Conversely, loss of Spalt4 function in the otic placode results in abnormal otic vesicle development. Intriguingly, Spalt4 appears to initiate a placode program appropriate for the axial level but is not involved in later development of specific placode fates. Fgfs can regulate Spalt4, since implantation of Fgf2 beads into the area opaca induces its expression. The results suggest that Spalt4 is involved in early stages of placode development, initiating cranial ectodermal invagination and region-specific gene regulatory networks.

The peripheral sensory nervous system in the vertebrate head: A gene regulatory perspective

“…Surprisingly, genes previously considered as neural crest specifiers like FoxD3 and N-myc are transiently coexpressed with pre-neural transcripts before being confined to the neural crest domain (Khudyakov and Bronner-Fraser, 2009) suggesting that at early stages a common regulatory state may define progenitors for both lineages. In addition to Pea3, the Ets transcription factor Erm is now also present in the forming neural plate and the surrounding ectoderm (Lunn et al, 2007) as are Zic1-5 (Elms et al, 2004;Elms et al, 2003;Gamse and Sive, 2001;Inoue et al, 2007;Merzdorf, 2007;Mizuseki et al, 1998;Nakata et al, 1997Nakata et al, , 1998, Dlx3 (in chick; Khudyakov and Bronner-Fraser, 2009), Sall1 (Bohm et al, 2008;Sweetman et al, 2005) and Spalt4 (or Sall4; Barembaum and Bronner-Fraser, 2007). In Xenopus, Zic1 and Zic5 are activated at the edge of the neural plate in response to FGF signalling presumably from the underlying paraxial mesoderm (Hong and Saint-Jeannet, 2007;Monsoro-Burq et al, 2003); in tissue recombination assays paraxial mesoderm can induce Zic5 in animal caps, but this is blocked in caps injected with dominant negative FGF receptor (Monsoro-Burq et al, 2003).…”

Do vertebrate neural crest and cranial placodes have a common evolutionary origin?

“…(71)(72)(73) Taken together, this suggests that cell shape changes in placodes and neural crest cells are under largely different genetic control although much remains to be learned about the regulatory networks controlling morphogenetic movements in each case.…”

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

“…4B; ; see also Khatri et al, 2014), whereas a small group of transcripts [ Irx5 , Lmx1a , cMyb (Betancur et al, 2011), Prdm1 , Sall4 (Barembaum and Bronner-Fraser, 2007), Sox13 , Zbtb16 and Znf385c ] becomes upregulated together with Pax2 and Etv4 (Figs 2, 4; ). Sox10 expression is initiated around 10ss together with Foxg1 and Dlx3 (Betancur et al, 2011; Khudyakov and Bronner-Fraser, 2009; Yang et al, 2013), and Prdm1 becomes restricted to the epibranchial territory (Fig.…”

“…In addition, Etv4 activates other early OEP transcripts ( Irx5 , Prdm1 , Zbtb16 , Sall4 , Sox8 ; Fig. 5A-F; Barembaum and Bronner-Fraser, 2007; Yang et al, 2013), and is also required for genes present at placode stages ( Lef1 , Lmx1b , Sox10 , Tcf4 ; ). In contrast, Etv4 represses some PPR genes ( Six1 , Eya2 ), the OEP factor Znf385c and late otic placode transcripts ( Tead3 , Arid3 , Sall1 ; …”

“…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.…”