An essential role for heat shock transcription factor binding protein 1 (HSBP1) during early embryonic development

Binnur Eroglu, Jin Na Min, Yan Zhang, Edyta Szurek, Dimitrios Moskofidis, Ali Eroglu, Nahid F Mivechi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Heat shock factor binding protein 1 (HSBP1) is a 76 amino acid polypeptide that contains two arrays of hydrophobic heptad repeats and was originally identified through its interaction with the oligomerization domain of heat shock factor 1 (Hsf1), suppressing Hsf1's transcriptional activity following stress. To examine the function of HSBP1 in vivo, we generated mice with targeted disruption of the hsbp1 gene and examined zebrafish embryos treated with HSBP1-specific morpholino oligonucleotides. Our results show that hsbp1 is critical for preimplantation embryonic development. Embryonic stem (ES) cells deficient in hsbp1 survive and proliferate normally into the neural lineage in vitro; however, lack of hsbp1 in embryoid bodies (EBs) leads to disorganization of the germ layers and a reduction in the endoderm-specific markers (such as α-fetoprotein). We further show that hsbp1-deficient mouse EBs and knockdown of HSBP1 in zebrafish leads to an increase in the expression of the neural crest inducers Snail2, Tfap2. α and Foxd3, suggesting a potential role for HSBP1 in the Wnt pathway. The hsbp1. -deficient ES cells, EBs and zebrafish embryos with reduced HSBP1 levels exhibit elevated levels of Hsf1 activity and expression of heat shock proteins (Hsps). We conclude that HSBP1 plays an essential role during early mouse and zebrafish embryonic development.

Original languageEnglish (US)
Pages (from-to)448-460
Number of pages13
JournalDevelopmental Biology
Volume386
Issue number2
DOIs
StatePublished - Feb 15 2014

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Keywords

  • Embryonic stem cells
  • HSBP1
  • Knockout mice
  • Neural crest
  • Zebrafish

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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