Heat shock factor

DEVELOPMENTAL BIOLOGY

Oocyte and Embryonic development

See the embryonic expression pattern of Hsf at the Berkeley Drosophila Genome Project Patterns of Gene Expression Site.

Hsp70 is a broadly conserved thermotolerance factor, but inhibits growth at normal temperatures and cannot be induced in early embryos. In Drosophila embryos the temporal and spatial patterns of Hsp70 inducibility are unexpectedly complex, with striking differences between the soma and the germline. In both, regulation occurs at the level of transcription. During the refractory period for Hsp70 induction, HSF (heat-shock transcription factor) exhibits specific DNA-binding activity characteristic of activation in extracts of heated embryos. Remarkably, however, HSF is restricted to the cytoplasm in intact embryos even after heat shock. It was surprising to find HSF located in the cytoplasm of early embryos since in virtually all organisms and cell types studied to date HSF is constitutively nuclear. HSF moves from the cytoplasm to the nucleus in the absence of heat precisely when the capacity to induce Hsp70 is acquired (cycle 12 of the germline, cycle 13 in the soma). During oogenesis, Hsp70 inducibility is lost in nurse cells around stage 10, in a posterior-to-anterior gradient and HSF redistributes from nucleus to cytoplasm in the same spatiotemporal pattern. In general, HSF is nuclear before stage 10 and cytoplasmic after stage 11, but the precise timing of relocation varies. Notably, when relocalization occurs, it exhibits a sharp spatial gradient, with the nurse cells more proximal to the oocyte showing cytoplasmic localization first, while distal cells still display nuclear concentration. Oocyte nuclei seem to follow the same pattern as nurse cell nuclei, but because the vitelline membrane forms at stage 10, they could not be scored in all egg chambers. In a highly inbred derivative of the Samarkind strain, HSF moves into embryonic nuclei earlier than in the standard wild-type strain. Correspondingly, Hsp70 is inducible earlier, confirming that nuclear transport of HSF controls the inducibility of Hsp70 in early embryos. Also reported for the first time are the nuclear import patterns of two general transcription factors: RNA polymerase subunit Ilc and TATA binding protein (TBP). Both enter nuclei in a highly synchronous manner, independent of each other and of HSF. The import of TBP coincides with the first reported appearance of transcripts in the embryo. It is suggested that the potentiation of general and heat shock-specific transcription in Drosophila embryos is controlled by the developmentally programmed relocalization of general and heat shock-specific transcription factors. Restricted nuclear entry of HSF represents a newly described mechanism for regulating the heat-shock response. Therefore, hyper-phosphorylation is not an obligate precondition for the activation of Hsp70 in response to heat (Wang, 1998).

Effects of Mutation or Deletion

The single-copy Drosophila hsf is located between the genes staufen and Polycomblike at cytological position 55A. Mutations were isolated in hsf. All four hsf mutations isolated arrest at the 1st or 2nd larval instar stage of development. The temperature sensitive hsf4 allele fails to respond to high temperature. The inability to activate expression of hsp (heat shock protein) genes may be attributed to the attenuation of DNA-binding activity at temperatures that induce hsp genes with wild type hsf. The mutant HSF is able to respond to recovery from anoxia, an alternative inducer of the heat shock response. Inability of hsf4 to induce a hsp response also correlates with a compromised thermotolerance in the hsf4 mutant. The hsf4 mutant exhibits a single temperature-sensitive period from 1.5 to 2.5 days of development, corresponding to the 1st and 2nd larval instars. Upon eclosion, adults are viable and fertile at 29 degrees C. Thus, a requirement for HSF function, as defined by the hsf4 mutant, appears to be restricted to early larval development. Expression of HSP26, HSP70 and HSP83 is unaltered in hsf4 animals during the temperature sensitive period at the non-permissive temperature. These results are consistent with studies indicating that the developmental expression of HSPs is essentially independent of HSEs. It is concluded, therefore, that the essential developmental function of HSF may involve the regulation of novel, non-heat shock genes. There is no obvious morphological defect in mutant larvae (Jedlicka, 1997)

Oogenesis is arrested in hsf1, hsf2 and hsf3 mutant females, but not in hsf4 mutant females. Either the HSF4 mutant protein retains a residual amount of activity at higher temperature that is sufficient for normal oogenesis but not for larval development, or, alternatively, the hsf4 mutation disrupts a function only required in larval development. The hsf mutant phenotype resembles that of ovo phenotype. The hsf1 mutation affects neither germ-line stem cell divisions that yield the 16-cell cyst, nor the differentiation of this cyst into nurse cells and the oocyte. The only observable defect in hsf1 egg chambers is that the DNA content of the nurse cells appears somewhat low, suggesting a possible defect in the endoreplication that normally occurs in these cells. Thus, HSF is required in the female germ-line for development of the egg chamber, at a stage after formation and differentiation of the germ-line cyst, but prior to vitellogenesis. The requirement for HSF in oogenesis also does not appear to be related to the regulation of HSP expression. HSP83 is expressed in developing hsf1 mutant egg chambers. The timing of HSP26,and HSP28 expression during oogenesis does not coincide with the temporal requirement for HSF; moreover, the expression of HSP26 in the ovary has been shown to be HSE independent. It is concluded that the two developmental functions of HSF are genetically separable and appear not to be mediated through the induction of HSPs (Jedlicka, 1997).

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date revised: 30 July 2006

 

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