Vulva development in Pristionchus pacificus

The formation of the vulva, the egg-laying structure of nematode females and hermaphrodites, has been at the center of our research activities over many years. We have developed the nematode vulva as a suitable „case study“ in evolutionary developmental biology and have obtained mechanistic insight into the evolutionary alterations of developmental processes by comparing P. pacificus to C. elegans. Basically, I study P. pacificus vulva formation with a group of graduate students by using a developmental genetic approach. Our comparative analysis can provide insight into the patterns and processes shaping evolutionary changes. The major differences in vulva cell fate specification between P. pacificus and C. elegans can be summarized as follows:

1. Non-vulval ventral epidermal cells die of programmed cell death in P. pacificus, but fuse with the hypodermis in C. elegans (Eizinger & Sommer, 1997).
2. The size of the vulva equivalence group in P. pacificus is reduced in comparison to C. elegans by the specific cell death of two anterior epidermal cells, P3.p and P4.p (Sommer & Sternberg, 1996).
3.  Vulva induction by the gonad is a 1-step process in C. elegans and relies on the anchor cell (AC), whereas it depends on a continuous interaction between the somatic gonad and the epidermis in P. pacificus (Sigrist & Sommer, 1999).
4.  A negative signaling system that involves the vulva precursor cells counteracts vulva induction in P. pacificus and prevents ectopic vulva differentiation (Zheng, 2005).
   
   

Large-scale mutagenesis screens for vulva-defective mutants have been carried out in P. pacificus and more than 100 mutants that constitute around 20 complementation groups have been isolated. The key results of our studies can be summarized as follows:

1) The size of the vulva equivalence group is regulated by a HAIRY/GROUCHO module in P. pacificus, which has no counterpart in C. elegans. Genetic and biochemical  studies show that HAIRY/GROUCHO regulate the expression of the Hox gene Ppa-lin-39 (Schlager et al., 2006).

2) Vulva induction in P. pacificus relies on Wnt signaling, rather than EGF signaling as in C. elegans. Thus, a different regulatory mechanism is employed in two nematodes to induce the formation of a homologous structure.
 (Tian et al., Curr. Biol. 2008)

3) The change of signaling pathway is not associated with copy number variations in Wnt or EGF signaling genes, i.e. ligand and receptor-encoding genes.
(Dieterich et al., Nat. Genet. 2008)

4) Also, the change of signaling pathway is not associated with differences in expression patterns.
(Tian et al., Curr. Biol. 2008)

5) Rather, P. pacificus has a novel regulatory linkage with an antagonism between Frizzled and Ryk type receptors for Wnt signal transduction.
(Wang & Sommer, PLoS Biology, 2011)

6) The evolution of small peptide domains in P. pacificus LIN-18/Ryk receptors is crucial for the evolutionary change in vulva development.
(Wang & Sommer, PLoS Biology, 2011)


Scientists involved:

Simone Kienle, Ph.D. Student

Introductory Reading:

Wang, X. & Sommer, R.J. (2011): Antagonism of LIN-17/Frizzled and LIN-18/Ryk in nematode vulva induction reveals evolutionary alterations in core developmental pathways. PLoS Biol 9(7): e1001110. doi:10.1371/journal.pbio.1001110.

Tian, H; Schlager, B., Xiao, H. & Sommer, R. J. (2008): Wnt signaling by differentially expressed Wnt ligands induces vulva development in Pristionchus pacificus. Current Biology, 18, 142-146.

Yi, B. & Sommer, R. J. (2007): The pax-3 gene is involved in vulva formation in Pristionchus pacificus and is a target of the Hox gene lin-39. Devolopment, 134, 3111-3119.

Schlager, B., Röseler, W., Zheng, M., Gutierrez, A & Sommer, R. J. (2006): HAIRY-like transcription factors and the evolution of the nematode vulva equivalence group. Current Biology, 16, 1386-1394.

Zheng, M., Messerschmidt, D., Jungblut, B. and Sommer, R. J. (2005): Conservation and diversification of Wnt signaling function during the evolution of nematode vulva development. Nature Genetics 37, 300-304.

Jungblut, B. and Sommer, R. J. (2000): Novel cell-cell interactions during vulva development in Pristionchus pacificus. Development, 127, 3295-3303.

Sigrist, C. B. & Sommer, R. J. (1999): Vulva formation in Pristionchus pacificus relies on continuous gonadal induction. Development, Genes and Evolution 209, 451-459.

Eizinger, A. & Sommer, R. J. (1997): The homeotic gene lin-39 and the evolution of nematode epidermal cell fates. Science, 278, 452-455.

Sommer, R. J. & Sternberg, P. W. (1996): Apoptosis limits the size of the vulval equivalence group in Pristionchus pacificus: a genetic analysis. Current Biology 6, 52-59.