foxQ2 evolved a key role in anterior head and central brain patterning in protostomes

Abstract

This is true for the two major lineages of bilaterian animals, the deuterostomes (including sea urchin 35 and humans) and protostomes (including annelids and insects) and the cnidarians (e.g. the sea 36 anemone), which are representatives of more ancient animals. However, the interaction of these 37 genes has been studied in deuterostomes and cnidarians but not in protostomes. Here, we present 38 the first study the function of the gene foxQ2 in protostomes. We found that the gene acts at the top 39 level of the genetic network and when its function is knocked down, the labrum (a part of the head) 40 and higher order brain centers do not develop. This is in contrast to the other animal groups where 41

cis‐Regulatory analysis for later phase of anterior neuroectoderm‐specific foxQ2 expression in sea urchin embryos

“…Amphioxus embryos also show earlier onset of foxQ2 expression (Kozmik et al, 2007;Yu et al, 2003). The foxQ2 expression in the six3/6-free region has also been reported in protostomes (Kitzmann et al, 2017;Marlow et al, 2014;Martín-Durán et al, 2015;Santagata et al, 2012). In addition, a recent study of embryos of another echinoderm (starfish) has reported that Six3 knockdown-embryos still express foxQ2 at the gastrula stage (Cheatle Jarvela, Yankura, & Hinman, 2016), although it is possible that the regulatory relationship was modified after the diversification of sea urchin and starfish.…”

“…By contrast, little is known about the positive regulation of foxQ2 . Previous analyses have suggested that Six3/6 contributes to the activation of foxQ2 in sea urchin Strongylocentrotus purpuratus (Wei, Yaguchi, Yaguchi, Angerer, & Angerer, ), red flour beetle (Kitzmann et al, ), and sea anemone (Sinigaglia et al, ), but the Six3/6‐mediated regulation is not sufficient to explain the expression pattern of foxQ2 in some cases. In fact, in sea urchin embryos, the onset of six3/6 expression seems to be later than that of foxQ2 (Materna, Nam, & Davidson, , our unpublished data), and expression domains of six3/6 and foxQ2 become separated at the later stage (Howard‐Ashby et al, ; Wei et al, ; Yaguchi et al, ).…”

“…In sea urchin embryos, the anterior neuroectoderm (so‐called animal plate [AP]) differentiates into multiple cell types including serotonergic neurons and apical tuft, and FoxQ2 plays the central role in the specification of these cells through the activation of the downstream genes such as fez , zfhx1 , and ankAT‐1 (Yaguchi et al, , ; Yaguchi, Angerer, Inaba, & Yaguchi, ; Yaguchi, Takeda, Inaba, & Yaguchi, ; Yaguchi, Yaguchi, Angerer, & Angerer, ). In the red flour beetle Tribolium , inhibition of foxQ2 by RNAi leads to the reduction or loss of the anterior head structure (Kitzmann et al, ). Even in cnidarians, one of the foxQ2 genes, foxQ2a , shows polarized expression in the opposite site of the blastopore (Figure a), and morpholino‐based knockdown of FoxQ2a causes reduction of the apical organ region (Chevalier, Martin, Leclère, Amiel, & Houliston, ; Sinigaglia et al, ).…”

“…Some vertebrates, however, lack the gene; fish and duck‐billed platypus possess FoxQ2, but eutherian mammals seem to have lost it (Mazet, Yu, Liberles, Holland, & Shimeld, ; Yu et al, ; Yu, Holland, & Holland, ); no foxQ2 genes also have been identified from chick and frog as far as we know. The expression of foxQ2 has been commonly observed in the anterior neuroectoderm of a wide variety of bilaterian embryos examined, for example, echinoderms (Tu et al, ; Yankura, Martik, Jennings, & Hinman, ), hemichordates (Fritzenwanker et al, ), amphioxus (Yu et al, ), ecdysozoans (Hunnekuhl & Akam, ; Kitzmann, Weißkopf, Schacht, & Bucher, ; Lee & Frasch, ), and spiralians (Marlow et al, ; Martín‐Durán et al, ; Santagata et al, ). Previous studies have demonstrated that FoxQ2 is required for anterior neuroectoderm formation.…”

“…Previous analyses have suggested that Six3/6 contributes to the activation of foxQ2 in sea urchin Strongylocentrotus purpuratus (Wei, Yaguchi, Yaguchi, Angerer, & Angerer, 2009), red flour beetle (Kitzmann et al, 2017), and sea anemone (Sinigaglia et al, 2013), but the Six3/6-mediated (a) The diagram shows the relationship of animals and illustrations of spatial foxQ2 expression in the embryos. The anterior pole is located at the top in the illustrations of bilaterian embryos, and the aboral pole is located at the top in those of the cnidarian embryo.…”