Heat shock transcription factor 1 (HSF1) is the main regulator of the stress response that triggers the transcription of several genes encoding heat shock proteins (Hsps). Hsps act as molecular chaperones involved in protein folding, stability, and trafficking. HSF1 is highly expressed in oocytes and Hsf1 knock-out in mice revealed that in the absence of stress this factor plays an important role in female reproduction. We previously reported that Hsf1؊/؊ females produce oocytes but no viable embryos. Consequently, we asked whether oocytes require HSF1 to regulate a particular set of Hsps necessary for them to develop. We find that Hsp90␣ (Hspaa1) is the major HSF1-dependent chaperone inasmuch as Hsf1 knock-out resulted in Hsp90-depleted oocytes. These oocytes exhibited delayed germinal vesicle breakdown (or G 2 /M transition), partial meiosis I block, and defective asymmetrical division. To probe the role of Hsp90␣ in this meiotic syndrome, we analyzed meiotic maturation in wildtype oocytes treated with a specific inhibitor of Hsp90, 17-allylamino-17-demethoxy-geldanamycin, and observed similar defects. At the molecular level we showed that, together with these developmental anomalies, CDK1 and MAPK, key meiotic kinases, were significantly disturbed. Thus, our data demonstrate that HSF1 is a maternal transcription factor essential for normal progression of meiosis.In mammals there are several heat shock factors (HSF1, -2, and -4) 3 that share a similar DNA binding domain, but HSF1 appears to be the major transcriptional regulator responsible for the stress-inducible expression of heat shock proteins (Hsps) (1, 2). The Hsf1 gene was targeted by homologous recombination in murine ES cells, and Hsf1 knock-out mice were produced by three different laboratories (3-5). Gene expression analyses in various cell types, and organs derived from these Hsf1 Ϫ/Ϫ mice revealed that HSF1 also regulates Hsp in physiological conditions (6 -8), providing accumulating evidence for the important function of HSF1 in maintaining cell homeostasis. Furthermore, those analyses and genome-wide screen demonstrated that numerous genes that were not classified as Hsps appeared to be HSF1-dependent (8, 9). Thus, HSF1 is clearly not restricted to the control of Hsp expression or the heat shock response. As shown by the complex phenotype of Hsf1 knock-out mice, HSF1 is involved in several specialized cell functions (e.g. placenta formation, immunity, placode development, cancer cell viability) (3, 5, 10, 11) and is essential for female reproduction (3). We showed previously that Hsf1 Ϫ/Ϫ female infertility is linked to the inability of Hsf1 Ϫ/Ϫ oocytes to produce viable embryos after natural mating (12). Nevertheless, the molecular and cellular mechanisms affected by the loss of HSF1 function in oocytes required further investigation to be better understood.Because HSF1 is highly expressed in oocytes, we hypothesized that it could regulate critical Hsps for the final development of oocytes into embryos. Although a series of studies separately ...

Members of the Tshz gene family encode putative zinc fingers transcription factors that are broadly expressed during mouse embryogenesis. Tshz1 is detected from E9.5 in the somites, the spinal cord, the limb buds and the branchial arches. In order to assess the function of Tshz1 during mouse development, we generated Tshz1-deficient mice. Tshz1 inactivation leads to neonatal lethality and causes multiple developmental defects. In the craniofacial region, loss of Tshz1 function leads to specific malformations of middle ear components, including the malleus and the tympanic ring. Tshz1(-/-) mice exhibited Hox-like vertebral malformations and homeotic transformations in the cervical and thoracic regions, suggesting that Tshz1 and Hox genes are involved in common pathways to control skeletal morphogenesis. Finally, we demonstrate that Tshz1 is required for the development of the soft palate.