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

Area of Science:

• Developmental Biology
• Genetics
• Neuroscience

Background:

• Anencephaly is a fatal human neural tube defect (NTD) characterized by an open anterior neural tube.
• Zebrafish models with reduced Nodal signaling exhibit an anencephaly-like phenotype.
• Nodal signaling is hypothesized to induce head mesendoderm and mesoderm, which are essential for neuroepithelial polarization and closure.

Purpose of the Study:

• To identify genes and pathways involved in anterior neurulation.
• To elucidate the mechanism by which Nodal signaling promotes the formation of a closed anterior neural tube.
• To investigate the roles of Wnt, FGF, and BMP signaling in this process.

Main Methods:

• Comparative transcriptome analysis of zebrafish embryos treated with a Nodal signaling inhibitor at different developmental stages (sphere vs. 30% epiboly).
• Pharmacological inhibition of FGF-receptor function.
• Analysis of gene expression related to cell junctions and signaling pathways.

Main Results:

• Over 3,000 transcripts potentially involved in anterior neurulation were identified.
• Reduced expression of genes encoding tight and adherens junction components was observed, supporting Nodal's role in neuroepithelial formation.
• Differential expression of Wnt, FGF, and BMP signaling pathway genes was noted.
• FGF-receptor inhibition induced an open anterior NTD and loss of mesodermal derivatives.

Conclusions:

• Nodal signaling is essential for anterior neural tube closure in zebrafish, analogous to anencephaly in humans.
• Both Nodal and FGF signaling pathways are critical for anterior neurulation, likely through the induction of head mesoderm.
• The findings highlight the complex interplay of signaling pathways in vertebrate embryonic development and the formation of the central nervous system.