Molecules in focus
No backbone but lots of Sox: Invertebrate Sox genes

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Abstract

Sox transcription factors are intimately involved in the development of multicellular organisms and accordingly understanding the role Sox genes play in diverse species of metazoans will hopefully shed light on the evolution of multicellularity. Here we review our current knowledge of the Sox genes isolated and characterised in invertebrates, ranging from the very simplest organisms through to complex chordates. While Sox genes have been identified in many invertebrate species, comparatively little is known about their functions outside the well-studied models, Drosophila, sea urchin and nematode. Consequently, we centre this review around the Sox family in Drosophila, comparing this with what is known about orthologous genes in other invertebrate species. We highlight several conserved themes that emerge when looking at the roles Sox proteins appear to play during embryogenesis, including early functions in CNS development and widespread interactions with the Wnt signalling pathway. Comparing the expression of Sox genes in insect species, where genome organisation is conserved but expression is apparently not, highlights the need for more functional data on the roles that related Sox proteins play in organisms outside the well-characterised models.

Section snippets

The Sox family in invertebrates

Invertebrates make up the vast majority of multicellular animal species on Earth and although arthropods, particularly insects, may be the most studied there are many other phyla within the group. While the phylogeny of the animals is undergoing constant revision (e.g. see Adoutte et al., 2000), at a basic level we can subdivide the extant species into three major groups: parazoa, the basal metazoans (sponges and placozoans) that have differentiated cell types but no tissues or body axis

The insects

Wilson and Dearden have most recently described the Sox genes of the sequenced insects and we refer readers to this work for specific details of protein alignments (Wilson and Dearden, 2008). Much of the analysis of Sox genes and their functions has focused on the fruit fly D. melanogaster, with a survey of Sox genes based on the first draft of the genome sequence (Cremazy et al., 2001) indicating eight Sox proteins encoded in the fly genome: four Group B genes and one each representing Groups

The Drosophila model

While there is an expanding list of invertebrate species in which Sox genes have been identified, unfortunately our knowledge of Sox function is largely restricted to Drosophila. Although the fly has proved to be an excellent model for understanding conserved aspects of transcription factor biology, it must be remembered that Drosophila is a highly specialised fly and may not be entirely representative of other insects never mind other invertebrates (Hughes and Kaufman, 2000). Bearing this in

Group B

There are four Group B genes in Drosophila: SoxNeuro (SoxN), Dichaete (D), Sox21a and Sox21b. In the vertebrates, the Group B genes can be differentiated into two subgroups, B1 and B2, both on the basis of their HMG-domain sequences and their functional properties (Bowles et al., 2000, Uchikawa et al., 1999). However, the utility of this subdivision in the insects is still not clear: while SoxN unambiguously groups with the vertebrate Sox1–3 proteins in all published alignments (Bowles et al.,

Dichaete and SoxNeuro

As with the vertebrates, Drosophila Group B genes have extensive and complex roles in the specification and development of the central nervous system but they also play critical roles in the development of other tissues. Although Dichaete is expressed in the female germline, transcripts or protein are not maternally contributed to the egg (Mukherjee et al., 2006). The early zygotic expression of Dichaete is reminiscent of both gap and pair-rule segmentation genes, since it is initially

Sox21a and Sox21b

As described above, both these Group B Sox genes are linked to Dichaete in a complex that is conserved across the sequenced insects (Fig. 2; McKimmie et al., 2005, Wilson and Dearden, 2008). While it was initially suggested that Sox21a represented a pseudogene, subsequent analysis shows that it is expressed in the anlage of the foregut and hindgut as well as some unidentified midline cells late in development: identical expression patterns are found in D. pseudoobscura (McKimmie et al., 2005).

Group B in other invertebrates

In all of the bilaterians that have been examined to date, at least one Group B Sox gene is expressed in the neurogenic region of the embryo from early in development. This includes the honeybee AmSoxB1 gene, where expression is found in the cephalic and trunk neuroectoderm as well as in the ventral midline: a composite of SoxN and Dichaete expression (Wilson and Dearden, 2008). Similar expression of a Group B gene is reported the millipede, G. marginata (GmSoxB1; Pioro and Stollewerk, 2006).

Group C

The Drosophila Sox14 gene and its orthologues in the other sequenced insects represents Group C (Sparkes et al., 2001, Wilson and Dearden, 2008). It is ubiquitously expressed throughout embryogenesis, but during the later stages of larval/pupal life and in adults it is prominent in the digestive system (Cremazy et al., 2001, Chintapalli et al., 2007). There are no reported mutations in Sox14 and no hits have been reported in cell-based RNAi screen. As far as we are aware, there are no current

Group D

Sox102F resides on the tiny fourth chromosome of D. melanogaster and is expressed relatively late during embryogenesis in the brain and a few cells of the ventral CNS (Cremazy et al., 2001). To date there is no published work on Sox102F, though we have used inducible RNAi constructs to examine Sox102F phenotypes in the CNS. We find sever disruptions in CNS morphology, particularly when the RNAi is expressed in glial cells. We also observe moderate defects in the CNS when Sox10F is overexpressed

Group E

The Drosophila Sox100B gene is the orthologue of vertebrate Sox8, 9, 10 and is dynamically expressed during embryogenesis in the gut, Malpighian tubules (fly kidneys), anal pad and gonads (Loh and Russell, 2000). The protein is also found in posterior mesodermal cells that contribute to the gonad, and while expression is initially in both sexes it becomes restricted to the male-specific somatic gonadal precursors (msSGPs). These are a cluster of cells at the posterior end of the coalescing

Group F

Sox15, the sole Drosophila Group F gene is expressed in a subset of the embryonic PNS, most likely in mechanoreceptor socket cells, and in the proximal portions of the third instar larval leg and wing imaginal discs (Cremazy et al., 2001). The gene has recently been the subject of two functional studies, which demonstrate that Sox15 null mutants are pupal lethal: any embryonic phenotypes are not reported. One study focused on the role of Sox15 in the PNS of imaginal discs and demonstrates a

Other Sox genes

As we note above, cnidarian and ctenophoran genomes contain Sox genes that are not easily classified into the established subgroups, however, in common with other Sox genes they are dynamically and tissue-specifically expressed. For example, the unclassified genes PpiSOX2 and PpiSOX21 from the comb jelly appear to be paralogous and show identical expression patterns in the apical sense organ, tentacles and adult sensory structures (Jager et al., 2008) and three of the unclassified Sox genes

Moving forward

Although the sequence relationships between the invertebrate Sox genes seem reasonably clear, the functional homologies are far less certain, particularly within the insects. While we only have functional data for Drosophila genes the expression data from honeybee indicates very little conservation apart from the neural expression of SoxN/AmSoxB1. Thus we believe it is critical that, at the very least, expression patterns of some of the Sox genes from other insects are determined. In

Acknowledgements

We apologise to the authors of any work we have neglected to mention in this review due to space constraints. We are indebted to Jelena Aleksic, Dean Baker, Lisa Meadows and John Roote for helpful comments on the manuscripts. Sox work in the Russell laboratory has been supported by research grants from BBSRC and MRC, NP is supported by a scholarship from the government of Thailand.

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