Development Genes and Evolution

, Volume 226, Issue 2, pp 99–107 | Cite as

vox homeobox gene: a novel regulator of midbrain-hindbrain boundary development in medaka fish?

  • Peter Fabian
  • Chrysoula N. Pantzartzi
  • Iryna Kozmikova
  • Zbynek Kozmik
Short Communication


The midbrain-hindbrain boundary (MHB) is one of the key organizing centers of the vertebrate central nervous system (CNS). Its patterning is governed by a well-described gene regulatory network (GRN) involving several transcription factors, namely, pax, gbx, en, and otx, together with signaling molecules of the Wnt and Fgf families. Here, we describe the onset of these markers in Oryzias latipes (medaka) early brain development in comparison to previously known zebrafish expression patterns. Moreover, we show for the first time that vox, a member of the vent gene family, is expressed in the developing neural tube similarly to CNS markers. Overexpression of vox leads to profound changes in the gene expression patterns of individual components of MHB-specific GRN, most notably of fgf8, a crucial organizer molecule of MHB. Our data suggest that genes from the vent family, in addition to their crucial role in body axis formation, may play a role in regionalization of vertebrate CNS.


Midbrain-hindbrain boundary vox medaka Heat shock element fgf8 Gene regulatory network 



We are grateful to Jindra Pohorela, Anna Zitova, Ivana Dobiasovska, and Vladimir Soukup for the technical support. We are grateful to Thomas Czerny for providing reagents and to Sarka Takacova for the manuscript proofreading. This work was supported by the Ministry of Education, Youth, and Sports (LO1419).

Supplementary material

427_2016_533_Fig5_ESM.gif (52 kb)
Fig. S1

vox expression is overlapping with otx2 expression in neural plate border and neural keel. (a-e´) Double RNA in situ hybridization for vox (purple) and otx2 (red). Dorsal views at stages 15 (a-d) and 17 (). Lateral view at stage 17 (e). Dashed line indicates position of the shield in the medaka embryo (a-d) or embryonic body (e, ). (b-d) Dissected shield area from (a). Arrowhead marks the edge of vox domain. (GIF 52 kb)

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High Resolution Image (TIF 2769 kb)
427_2016_533_Fig6_ESM.gif (149 kb)
Fig. S2

Knockdown of medaka vox by morpholino (MO). (a) Schematic drawing of the mRNA construct vox_aug_region-eGFP (b) mRNA construct with vox MO. Embryos injected with the synthetic mRNA alone () and with vox MO (). (c-f´) RNA in situ hybridization for otx2, en2, wnt1 and fgf8 genes on embryos injected with control MO (c-f) and vox morpholino (c´-f´). Embryos are shown, anterior to right, in (c-f´ top) lateral view, and (c-f´ bottom) dorsal view. Arrowheads mark developing MHB. (GIF 149 kb)

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High Resolution Image (TIF 6596 kb)
427_2016_533_Fig7_ESM.gif (83 kb)
Fig. S3

The effects of vox overexpression during early development. (a) mCherry:HSE:vox construct. (b) Experimental strategy used in this work. (c, ) overexpression of vox gene (c) and mCherry marker gene () after heat shock. (d-e´) Heat-treated control and mCherry:HSE:vox transgenic line embryos at stage 16. (d, d´) Heat shock does not seem to influence development of control embryos at later developmental stages (stage 30). (e, e´) Overexpression of vox during gastrulation affects development of mCherry:HSE:vox transgenic line embryos. Inset: MHB in detail. (GIF 82 kb)

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High Resolution Image (TIF 3807 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Peter Fabian
    • 1
  • Chrysoula N. Pantzartzi
    • 1
  • Iryna Kozmikova
    • 1
  • Zbynek Kozmik
    • 1
  1. 1.Institute of Molecular Genetics, Academy of Sciences of the Czech RepublicPrague 4Czech Republic

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