Towards a new understanding of the reproductive system: from non-coding RNAs to disease - Dagmar Wilhelm

Dr Dagmar Wilhelm

Our group focuses on the elucidation of regulatory mechanisms that control gene expression during embyronic development. One of the most amazing biological processes is the development of a fertilised egg into a complex organism. It involves the orchestration of cellular processes such as cell proliferation, migration, differentiation and apoptosis, which is controlled by a delicate network of gene regulation and interaction. Disturbance of this network caused by gene mutation or misexpression during development results in malformation and malfunction of organs, diseases such as cancer and often lethality. Therefore, each of these processes must involve a large number of regulatory mechanisms.

Until recently our work centred around the conventional dogma, which states that gene activity is controlled by transcription factor binding to proximal promoters and/or enhancers adjacent to genes. We are now extending these studies to include the fact that gene activity is also regulated post-transcriptionally by non-coding RNAs (ncRNAs), such as microRNAs. In addition to investigating the role of microRNAs during development, we have discovered a new class of ncRNAs, uaRNAs (3’UTR-associated non-coding RNAs) that display a highly regulated stage- and sex-specific expression pattern during embryogenesis.

In addition, we want to use knowledge of small RNA processing and function, also called RNA interference (RNAi) as a tool to control pest species in Australia. The common carp represents an increasing menace to Australian freshwater ecosystems. Further unchecked growth and spread of the carp population poses a threat to many native fish species. In this project we are investigating the biology of RNAi in carp and zebrafish to investigate the potential of a "daughterless" approach to make use of the endogeneous RNAi processing machinery to knock down aromatase and thereby control carp numbers.

Our research uses mouse and zebrafish as model systems and integrates molecular and developmental biology to study mechanisms of gene regulation by transcription factors as well as ncRNAs during embryonic development, concentrating on sex determination and gonad development but extending to other developmental systems such as chondrogenesis.


The aims of our research are to address the intersections of the following questions:

1.    What are the regulatory mechanisms underlying the development of the ovary?

2.    What are the roles of ncRNAs, including long and small RNAs, during the development of testes and ovaries?

3.    What are the processing and functional mechanisms of small RNAs in fish?


Research Projects

•    Characterising the role of miR-202 during embryonic development

•    Identification and analysis of novel microRNAs involved in gonad development

•    Functional characterisation of uaRNAs during embryonic development

•    Studying the cellular and molecular regulation of foetal ovary development

•    Characterisation of RNAi in fish

Key Publications


Wilhelm, D. (2007). R-spondin1 – the long-missing, female-determining gene? BioEssays 29: 314-318.

Wilhelm, D., Hiramatsu, R., Mizusaki, H., Widjaja, L., Combes, A.N., Kanai, Y., and Koopman, P. (2007). SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development. Journal of Biological Chemistry 282: 10553-10560.

Wilhelm, D., Palmer, S., and Koopman, P. (2007). Sex determination and gonadal development in mammals. Physiological Reviews 87: 1-28.

Wilhelm, D., and Koopman, P. (2006). The making of maleness: Towards an integrated view of male sexual development. Nature Reviews Genetics 7: 620-631.

Wilhelm, D., Martinson, F., Bradford, S., Wilson, M.J., Combes, A., Beverdam, A., Bowles, J., Mizusaki, H., and Koopman, P. (2005). Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signalling to activate Sox9 during mammalian sex determination. Developmental Biology 287: 111-124.

Wilhelm, D., and Englert, C. (2002). The Wilms tumour suppressor WT1 regulates gonadal development by activation of Sf1. Genes and Development 16: 1839-1851.

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