Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2017 Aug 01;11431:E6352-E6360. doi: 10.1073/pnas.1704194114.
Show Gene links
Show Anatomy links
Conserved gene regulatory module specifies lateral neural borders across bilaterians.
Li Y
,
Zhao D
,
Horie T
,
Chen G
,
Bao H
,
Chen S
,
Liu W
,
Horie R
,
Liang T
,
Dong B
,
Feng Q
,
Liu X
.
???displayArticle.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 neuroectodermlateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module (Msx/vab-15, Pax3/7/pax-3, and Zic/ref-2) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref-2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans, Drosophila melanogaster, and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1, which functions synergistically with Msx/vab-15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.
Fig. 6.
ZNF703/tlp-1 is a novel regulator functioning as an Msx/vab-15 modulator both in worm lateral neuroblasts and vertebrate NPB. (A) Embryonic expression of worm ZNF703/tlp-1. A comma-stage embryo carrying the Ptlp-1::H1::mCherry reporter trangene is shown. Arrowheads indicate P neuroblasts. Arrow indicates the mother cell of V5 and Q neuroblasts. (Scale bar, 10 μm.) (B–E) Phenotypes of ZNF703/tlp-1 and Msx/vab-15 mutant worms of migration and differentiation of lateral neuroblasts. The y axis represents the number of VD neurons recognized by the Punc-25::GFP marker (B) or the fraction of worms showing the specified defect (C–E). The number of scored worms is shown. (F) The expression of ZNF703 in Xenopus embryos from stage (st)12 to st19. (Scale bar, 0.5 mm.) The red dot lines represent the location of cross section. (G) Whole-mount in situ hybridization assay in Xenopus embryos (st16 to st17) to examine the effect of MO knockdown of Msx/vab-15 and/or ZNF703/tlp-1 on the expression of the neural plate marker Sox2, neural crest specifier FoxD3, and Rohon–Beard sensory neuron progenitor marker Runx1 and DRG progenitor marker Islet1. Asterisks indicate the injected side of an embryo. The red lines and green lines indicate the length of left and right parts of neural tubes, respectively. # indicates mRNA resistant to the ZNF703 MO. Fractions of scored embryos with phenotype are shown. (Scale bar, 0.5 mm.) Error bars represent standard errors.
Fig. S2.
Little effect on cell proliferation (A) and apoptosis (B) of Xenopus embryos by the moderate double knockdown of Msx/vab-15 and ZNF703/tlp-1. pH3, phosphorylated histone H3Serine10 as a cell proliferation marker. TUNEL, apoptosis marker. Embryos are viewed from the dorsal side with anterior on top. Asterisks indicate the morpholino injection side. (Scale bar, 0.5 mm.)
Fig. S3.
Assessment of effects of ZNF703 and Msx1 depletion in Xenopus. (A) Immunoblots (IBs) showing that ZNF703 MO efficiently blocks translation of an MO-complementary Znf703-HA mRNA but not an MO-resistant Znf703-HA# mRNA. (B) Immunoblots showing that Msx1 MO efficiently blocks translation of an MO-complementary Msx1-HA mRNA but not an MO-resistant Msx1-HA# mRNA. β-Actin serves as a loading control in A and B. (C) Depletion of ZNF703 alone through injecting a mix of MOs up to 40 ng has no discernable effects on the expression of foxd3, sox2, runx1, and islet. However, depletion of Msx1 using 10 to 15 ng MO discernably decreased the expression of foxd3, runx1, and islet1 and expanded the expression domain of sox2. Asterisks indicate the injected side of an embryo. (Scale bar, 0.5 mm.)
Abitua,
Identification of a rudimentary neural crest in a non-vertebrate chordate.
2012, Pubmed
Abitua,
Identification of a rudimentary neural crest in a non-vertebrate chordate.
2012,
Pubmed
Abitua,
The pre-vertebrate origins of neurogenic placodes.
2015,
Pubmed
Albertson,
The pharynx of Caenorhabditis elegans.
1976,
Pubmed
Arendt,
Comparison of early nerve cord development in insects and vertebrates.
1999,
Pubmed
Arendt,
The origin and evolution of cell types.
2016,
Pubmed
Coric,
Simple chordates exhibit a proton-independent function of acid-sensing ion channels.
2008,
Pubmed
D'Alessio,
msh may play a conserved role in dorsoventral patterning of the neuroectoderm and mesoderm.
1996,
Pubmed
Denes,
Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria.
2007,
Pubmed
Dickinson,
Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination.
2013,
Pubmed
Du,
Genes regulating touch cell development in Caenorhabditis elegans.
2001,
Pubmed
Duggan,
Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.
1998,
Pubmed
Duval,
Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord.
2014,
Pubmed
Feng,
Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression.
2013,
Pubmed
Fritzsch,
Molecular evolution of the vertebrate mechanosensory cell and ear.
2007,
Pubmed
Frøkjær-Jensen,
Random and targeted transgene insertion in Caenorhabditis elegans using a modified Mos1 transposon.
2014,
Pubmed
Gao,
A novel role for Ascl1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT.
2016,
Pubmed
,
Xenbase
Garnett,
BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border.
2012,
Pubmed
Gratz,
Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease.
2013,
Pubmed
Green,
Evolution of vertebrates as viewed from the crest.
2015,
Pubmed
Hejnol,
Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution.
2015,
Pubmed
Ho,
Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry.
2015,
Pubmed
Holland,
Chordate roots of the vertebrate nervous system: expanding the molecular toolkit.
2009,
Pubmed
Huang,
Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.
1994,
Pubmed
Imai,
Regulatory blueprint for a chordate embryo.
2006,
Pubmed
Isshiki,
The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.
1997,
Pubmed
Lander,
Interactions between Twist and other core epithelial-mesenchymal transition factors are controlled by GSK3-mediated phosphorylation.
2013,
Pubmed
,
Xenbase
Lin,
Pax3 and Pax7 interact reciprocally and regulate the expression of cadherin-7 through inducing neuron differentiation in the developing chicken spinal cord.
2016,
Pubmed
Liu,
Analysis of cell fate from single-cell gene expression profiles in C. elegans.
2009,
Pubmed
Lowe,
Dorsoventral patterning in hemichordates: insights into early chordate evolution.
2006,
Pubmed
Medeiros,
The evolution of the neural crest: new perspectives from lamprey and invertebrate neural crest-like cells.
2013,
Pubmed
Milet,
Neural crest induction at the neural plate border in vertebrates.
2012,
Pubmed
,
Xenbase
Murray,
Multidimensional regulation of gene expression in the C. elegans embryo.
2012,
Pubmed
Murray,
Automated analysis of embryonic gene expression with cellular resolution in C. elegans.
2008,
Pubmed
Nikitina,
Dissecting early regulatory relationships in the lamprey neural crest gene network.
2008,
Pubmed
Orgogozo,
FlyPNS, a database of the Drosophila embryonic and larval peripheral nervous system.
2005,
Pubmed
Petersen,
The prevalence of Caenorhabditis elegans across 1.5 years in selected North German locations: the importance of substrate type, abiotic parameters, and Caenorhabditis competitors.
2014,
Pubmed
Ramos,
msh/Msx gene family in neural development.
2005,
Pubmed
Reece-Hoyes,
Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns.
2007,
Pubmed
Rota-Stabelli,
Molecular timetrees reveal a Cambrian colonization of land and a new scenario for ecdysozoan evolution.
2013,
Pubmed
Satou,
Action of morpholinos in Ciona embryos.
2001,
Pubmed
Sauka-Spengler,
Ancient evolutionary origin of the neural crest gene regulatory network.
2007,
Pubmed
Schlosser,
The evolutionary history of vertebrate cranial placodes II. Evolution of ectodermal patterning.
2014,
Pubmed
,
Xenbase
Schlosser,
Do vertebrate neural crest and cranial placodes have a common evolutionary origin?
2008,
Pubmed
,
Xenbase
Sharman,
An amphioxus Msx gene expressed predominantly in the dorsal neural tube.
1999,
Pubmed
Shaye,
OrthoList: a compendium of C. elegans genes with human orthologs.
2011,
Pubmed
Shen,
Conditional knockouts generated by engineered CRISPR-Cas9 endonuclease reveal the roles of coronin in C. elegans neural development.
2014,
Pubmed
Stolfi,
Migratory neuronal progenitors arise from the neural plate borders in tunicates.
2015,
Pubmed
Strausfeld,
Introduction to 'Homology and convergence in nervous system evolution'.
2016,
Pubmed
Sulston,
Post-embryonic cell lineages of the nematode, Caenorhabditis elegans.
1977,
Pubmed
Sulston,
The embryonic cell lineage of the nematode Caenorhabditis elegans.
1983,
Pubmed
Thompson,
The Paired-box protein PAX-3 regulates the choice between lateral and ventral epidermal cell fates in C. elegans.
2016,
Pubmed
Waki,
Genetic pathways for differentiation of the peripheral nervous system in ascidians.
2015,
Pubmed
Wang,
Msx3: a novel murine homologue of the Drosophila msh homeobox gene restricted to the dorsal embryonic central nervous system.
1996,
Pubmed
Wrischnik,
The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.
1997,
Pubmed
Yang,
The role of a Drosophila POU homeo domain gene in the specification of neural precursor cell identity in the developing embryonic central nervous system.
1993,
Pubmed
Zhang,
NEDD4L regulates convergent extension movements in Xenopus embryos via Disheveled-mediated non-canonical Wnt signaling.
2014,
Pubmed
,
Xenbase
Zhao,
A transcription factor controlling development of peripheral sense organs in C. elegans.
1995,
Pubmed
Zhu,
A proneural gene controls C. elegans neuroblast asymmetric division and migration.
2014,
Pubmed
