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Proc Natl Acad Sci U S A
2017 Aug 01;11431:E6352-E6360. doi: 10.1073/pnas.1704194114.
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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
,
Tao 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.)
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