Abstract
One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryonic fields. To address this question, we focused on genes that are active in the anterior neuroectoderm and non-neural ectoderm of the ascidian Ciona intestinalis. Following the dissection of a prototypic anterior placodal enhancer, we searched all genomic conserved non-coding elements for duplicated motifs around genes showing anterior neuroectodermal expression. Strikingly, we identified an over-represented pentamer motif corresponding to the binding site of the homeodomain protein OTX, which plays a pivotal role in the anterior development of all bilaterian species. Using an in vivo reporter gene assay, we observed that 10 of 23 candidate cis-regulatory elements containing duplicated OTX motifs are active in the anterior neuroectoderm, thus showing that this cis-regulatory signature is predictive of neuroectodermal enhancers. These results show that a common cis-regulatory signature corresponding to K50-Paired homeodomain transcription factors is found in non-coding sequences flanking anterior neuroectodermal genes in chordate embryos. Thus, field-specific selector genes impose architectural constraints in the form of combinations of short tags on their target enhancers. This could account for the strong evolutionary conservation of the regulatory elements controlling field-specific selector genes responsible for body plan formation.
Highlights
The concept of ‘‘selector genes’’ was introduced 30 years ago by Garcia-Bellido to define genes that interpret a transient regulatory state and specify the identity of a given developmental field [1]
Regional identity in embryos is defined by a few specific transcription factors that activate a large number of target genes through binding to common tags in regulatory sequences
In chordates it is unclear if such tags can be identified in the cis-regulatory regions of regionally expressed genes. To address this question we focused on the anterior nervous system where Otx codes for a transcription factor that triggers expression of many other head-specific genes
Summary
The concept of ‘‘selector genes’’ was introduced 30 years ago by Garcia-Bellido to define genes that interpret a transient regulatory state and specify the identity of a given developmental field [1]. The question of how embryos execute distinct and unique differentiation programs using these selector genes can be tackled by focusing on how gene expression is encoded in cis-regulatory elements and their field-specific trans-acting factors (TF). In vertebrates as well as in flies, Crx and its Drosophila homolog Otd act through a small cis-regulatory motif overrepresented in the elements flanking the target genes [6,7,8,9,10] In addition to this evolutionary conserved network, many others in Caenorhabditis elegans and Drosophila melanogaster have shown that cell specific enhancers contain a common ‘‘tag’’ corresponding to a specific cis-regulatory motif, and that this motif is linked to one or a few terminal selector genes [11,12].
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