Identification of transcripts potentially involved in neural tube closure using RNA sequencing

Lexy M. Kindt, Alicia R. Coughlin, Tianna R. Perosino, Haley N. Ersfeld, Marshall E Hampton, Jennifer O Liang

Research output: Contribution to journalArticle

Abstract

Anencephaly is a fatal human neural tube defect (NTD) in which the anterior neural tube remains open. Zebrafish embryos with reduced Nodal signaling display an open anterior neural tube phenotype that is analogous to anencephaly. Previous work from our laboratory suggests that Nodal signaling acts through induction of the head mesendoderm and mesoderm. Head mesendoderm/mesoderm then, through an unknown mechanism, promotes formation of the polarized neuroepithelium that is capable of undergoing the movements required for closure. We compared the transcriptome of embryos treated with a Nodal signaling inhibitor at sphere stage, which causes NTDs, to embryos treated at 30% epiboly, which does not cause NTDs. This screen identified over 3,000 transcripts with potential roles in anterior neurulation. Expression of several genes encoding components of tight and adherens junctions was significantly reduced, supporting the model that Nodal signaling regulates formation of the neuroepithelium. mRNAs involved in Wnt, FGF, and BMP signaling were also differentially expressed, suggesting these pathways might regulate anterior neurulation. In support of this, we found that pharmacological inhibition of FGF–receptor function causes an open anterior NTD as well as loss of mesodermal derivatives. This suggests that Nodal and FGF signaling both promote anterior neurulation through induction of head mesoderm.

Original languageEnglish (US)
Article numbere23096
JournalGenesis
Volume56
Issue number3
DOIs
StatePublished - Mar 2018

Fingerprint

Neurulation
RNA Sequence Analysis
Neural Tube
Mesoderm
Anencephaly
Embryonic Structures
Neural Tube Defects
Head
Gene Components
Adherens Junctions
Tight Junctions
Zebrafish
Transcriptome
Pharmacology
Phenotype
Messenger RNA

Keywords

  • RNA sequencing
  • neural tube defects
  • neurulation
  • nodal
  • zebrafish

Cite this

Identification of transcripts potentially involved in neural tube closure using RNA sequencing. / Kindt, Lexy M.; Coughlin, Alicia R.; Perosino, Tianna R.; Ersfeld, Haley N.; Hampton, Marshall E; Liang, Jennifer O.

In: Genesis, Vol. 56, No. 3, e23096, 03.2018.

Research output: Contribution to journalArticle

Kindt, Lexy M. ; Coughlin, Alicia R. ; Perosino, Tianna R. ; Ersfeld, Haley N. ; Hampton, Marshall E ; Liang, Jennifer O. / Identification of transcripts potentially involved in neural tube closure using RNA sequencing. In: Genesis. 2018 ; Vol. 56, No. 3.
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