Conserved gene regulatory module specifies lateral neural borders across bilaterians.

Abstract

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier <i>Msx/vab-15</i> specifies lateral neuroblasts in <i>Caenorhabditis elegans</i> Second, orthologs of the vertebrate NPB specification module (<i>Msx/vab-15</i>, <i>Pax3/7/pax-3</i>, and <i>Zic/ref-2</i>) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of <i>Msx/vab-15</i> is more lateral than those of <i>Pax3/7/pax-3</i> and <i>Zic/ref-</i>2 in <i>C. elegans</i> Third, we show that <i>Msx/vab-15</i> regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including <i>C. elegans</i>, <i>Drosophila melanogaster</i>, and <i>Ciona intestinalis</i> We also identify a novel lateral neural border specifier, <i>ZNF703/tlp-1</i>, which functions synergistically with <i>Msx/vab-</i>15 in both <i>C. elegans</i> and <i>Xenopus laevis</i> These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.