Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation

Abstract

Canalization, also known as developmental robustness, describes an organism's ability to produce the same phenotype despite genotypic variations and environmental influences 1,2. In Drosophila, Hsp90, the Trithorax group proteins, and transposon silencing have been implicated in canalization 3,4. Despite this, molecular mechanism underlying canalization remains elusive. Here, using an Drosophila eye-outgrowth assay sensitized by the dominant Kr Irregular facets-1 (Kr If-1), allele 3 , we show that the piRNA pathway, but not siRNA or miRNA pathways, is involved in canalization. Furthermore, we isolated a protein complex composed of Hsp90, Piwi, and the Hsp70/Hsp90 Organizing Protein Homolog (Hop), and demonstrated the function of this complex in canalization. Our data indicate that Hsp90 and Hop regulate the piRNA pathway via Piwi to mediate canalization. Moreover, they point to epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization. In both plants and animals, Hsp90 buffers against morphological changes induced either by genetic or non-genetic mechanisms, thereby promoting the robustness of the developmental programs that have been subjected to natural selection 5-8. However, under certain conditions, such as environmental stress, Hsp90 becomes overwhelmed, loosens its grip on canalization, and fails to repress the expression of genotype variants that have accumulated during evolution. The expressed phenotypes quickly become independent of Hsp90 deficiency, can be inherited in later generations, and could be subject to natural selection 3,5. In addition to Hsp90, maternally inherited epigenetic machineries also prevent expression of Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Multiple roles for Piwi in silencing Drosophila transposons

“…Numerous studies have highlighted a role for Piwi in silencing transposons in Drosophila gonads (Kalmykova et al 2005;Saito et al 2006;Pelisson et al 2007;Yin and Lin 2007;Gangaraju et al 2011;Klenov et al 2011;Sokolova et al 2011). However, these have been based on genetic mutants, which lose Piwi function in both the germline and somatic compartments with consequent severe effects on ovary morphology.…”

The Protein Chaperone HSP90 Can Facilitate the Divergence of Gene Duplicates

“…Like other well-established clients, such as the Drosophila Argonaute Piwi and the human transcription factor HSF, BES1 was not degraded upon HSP90 inhibition ( Figure 1E) (Zou et al 1998;Gangaraju et al 2011). It appears that, while the hypophosphorylated form of BES1 accumulated upon HSP90 inhibition, it is nonfunctional (Figure 1, A-D).…”

Developmental functions of piRNAs and transposable elements

“…Genes of the piRNA pathway have also been implicated in several biological functions in somatic tissues, including heterochromatin formation, long-term memory and suppression of phenotypic variation (canalization). [75][76][77] These data suggest that piRNAs might be involved in many additional biological and developmental functions that are yet to be discovered. …”