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Etv2, a master regulator of endothelial cell fate, can induce fast skeletal muscle cells to transdifferentiate into endothelial cells in the zebrafish embryo.

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The heat shock transcription factor HSF1 regulates the stress-inducible expression of heat shock proteins (HSPs) and other molecular chaperones that are involved in higher order protein structure and assembly. HSPs protect organisms against environmental challenges. Targeted disruption of the murine Hsf1 gene results in massive heat-induced apoptosis in cells deficient in HSF1. To explore whether zebrafish HSF1 has overlapping function with mammalian HSF1, we inhibited zebrafish HSF1 expression during development using morpholino oligonucleotides specific for the HSF1 sequence. The zebrafish HSF1 morpholinos were injected at the one-to eight-cell-stage embryos of a transgenic zebrafish carrying an Hsp70-promoter-GFP (Hsp70-EGFP) reporter construct. The injected embryos were heated and analyzed for GFP expression and the presence of apoptotic cells 24 h after fertilization. Our data indicate that the morpholino-injected embryos exhibit a severe reduction in expression of the heat-induced HSP70-GFP reporter gene. Furthermore, there was an enhancement of apoptotic response in these transgenic zebrafish embryos at elevated temperatures. Thus, the function of HSF1 is conserved in zebrafish and higher vertebrates.Diverse organisms from bacteria to humans respond to environmental challenges that cause protein damage by synthesizing HSPs. HSPs protect cells and tissues against such challenges by assisting in the repair of protein damage, thereby protecting cells from self-destruction or apoptosis (Li and Mivechi, 1986;Mivechi et al., 1994;Mosser et al., 1997;Morimoto, 1998; L. Huang, N. F. Mivechi, and D. Moskophidis, unpublished data). The inducible regulation of HSP expression is achieved by heat shock transcription factors (HSFs). In lower organisms such as yeast and Drosophila, control of the heat shock response is accomplished by a single Hsf gene (Wu, 1995). In higher eukaryotes, however, there are multiple Hsf genes that respond to diverse environmental insults, suggesting that individual HSF proteins may be responsible for different biological functions (Morimoto, 1998). In zebrafish, at least two Hsf genes are expressed to encode multiple isoforms of each protein. cDNAs for HSF1a and HSF1b have been recently reported (Rabergh, 2000) and an EST clone for a second HSF family member with high homology with HSF2 has been deposited in the database. In this report, we have isolated and analyzed a unique isoform of HSF1 (designated thereafter as HSF1c) in zebrafish (Fig. 1A, B). In situ hybridization indicated that HSF1c was widely expressed throughout early development (Fig. 1C). Both the zebrafish HSF1a and HSF1c isoforms are capable of binding to the heat shock element (HSE), and their DNA binding abilities are enhanced if the in vitro translated HSF1a or HSF1c is incubated at elevated temperature (data not shown). HSF1 proteins in different species are highly conserved in the DNA binding domain and oligomerization domains. HSF1 exists as an inactive monomer under physiological conditions and acquires DNA binding ...