Transcriptome profiling of genes involved in neural tube closure during human embryonic development using long serial analysis of gene expression (long-SAGE)

Deidre R. Krupp, Pu Ting Xu, Sophie Thomas, Andrew Dellinger, Heather C. Etchevers, Michel Vekemans, John R. Gilbert, Marcy C. Speer, Allison E. Ashley-Koch, Simon G. Gregory

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

BACKGROUND: Neural tube defects (NTDs) are common human birth defects with a complex etiology. To develop a comprehensive knowledge of the genes expressed during normal neurulation, we established transcriptomes from human neural tube fragments during and after neurulation using long Serial Analysis of Gene Expression (long-SAGE). METHODS: Rostral and caudal neural tubes were dissected from normal human embryos aged between 26 and 32 days of gestation. Tissues from the same region and Carnegie stage were pooled (n ≥ 4) and total RNA extracted to construct four long-SAGE libraries. Tags were mapped using the UniGene Homo sapiens 17 bp tag-to-gene best mapping set. Differentially expressed genes were identified by chi-square or Fisher's exact test, and validation was performed for a subset of those transcripts using in situ hybridization. In silico analyses were performed with BinGO and EXPANDER. RESULTS: We observed most genes to be similarly regulated in rostral and caudal regions, but expression profiles differed during and after closure. In silico analysis found similar enrichments in both regions for biologic process terms, transcription factor binding and miRNA target motifs. Twelve genes potentially expressing alternate isoforms by region or developmental stage, and the microRNAs miR-339-5p, miR-141/200a, miR-23ab, and miR-129/129-5p are among several potential candidates identified here for future research. CONCLUSIONS: Time appears to influence gene expression in the developing central nervous system more than location. These data provide a novel complement to traditional strategies of identifying genes associated with human NTDs and offer unique insight into the genes associated with normal human neurulation.

Original languageEnglish (US)
Pages (from-to)683-692
Number of pages10
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume94
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Gene expression
  • Homo sapiens
  • Long-SAGE
  • Neural tube defects
  • Neurulation

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

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    Krupp, D. R., Xu, P. T., Thomas, S., Dellinger, A., Etchevers, H. C., Vekemans, M., Gilbert, J. R., Speer, M. C., Ashley-Koch, A. E., & Gregory, S. G. (2012). Transcriptome profiling of genes involved in neural tube closure during human embryonic development using long serial analysis of gene expression (long-SAGE). Birth Defects Research Part A - Clinical and Molecular Teratology, 94(9), 683-692. https://doi.org/10.1002/bdra.23040