(Symmetric ommatidia, both of the R3/R3- and R4/R4-type, in which an ommatidium adopts two cells of one fate and no cells of the other fate, are also seen in tissue polarity mutant eyes and will be discussed in the results).
shRNA depletion is genetically dominant, avoids labor-intensive sorting of mutant females, and will enable biochemical analysis in future work.
Each mouse genetics centre will participate in the production and phenotyping of mouse mutant lines, and will deposit the data into a Data Centre for analysis and dissemination (Fig. 1).
The observation that the Cx26 HCs purified from bacteria have similar properties than those expressed in eukaryotic cells indicates that the bacterial expression system will be useful to study the basic properties of wild-type and mutant HCs and will be a useful complement to others currently in use.
A simultaneous generation of two mutant cells (with mutations of a type relevant to the processes of interest) is possible, but it is a rare event compared to the production of only one mutant daughter cell, and will be neglected here.
The mutant and wild types will eventually meet, and only one type will then fill the remaining open terrain (this has been discussed in detail in Hallatschek et al. 2007).
Sequencing of more mutants and strains will be needed to address these questions.
Taking the example of DISC1, we know that the normal regulation of neural progenitor proliferation by modulation of GSK3beta/beta-catenin signaling is disrupted in DISC1 mutants and it will be interesting to see if the same process is disturbed by other mutations.
If the differences in gene content between the two recombinant chromosomes affect fitness, then the deletion mutant and duplication mutant will have different probabilities of evolutionary persistence.
Finally, the user can provide two alternative sequences (wildtype and mutant), and the system will determine the location of variants to be analyzed by comparing them.
