Much of what we know about gene interactions in development has been learned using nematodes, yeast, flies, and bacteria. This is due, in part, to the relative ease of genetic manipulation of these well-characterized genomes. However, of great interest are gene interactions involving complex diseases in humans. Wang and White [(2011). Nature Methods 8(4):341–346] describe work using RNAi to examine the interactive proteome in mammalian cells. They mention that knockdown inefficiencies and off-target effects of introduced RNAi species are areas that need particular improvement if the methodology is to be fruitful.
Comment on how 'knockdown inefficiencies' and 'off-target effects' would influence the interpretation of results.

Vulval development in C. elegans is dependent on the response of some of the central epidermal progenitor cells in the region of the developing vulva to a chemical signal from the gonad. Signaling from the gonad is blocked by action of the vulvaless mutant let-23 so that none of the central progenitor cells form vulval structures. In the vulvaless mutant, n300, the central progenitor cells do not form.

What phenotype (vulva formed or vulvaless) would you expect from the double mutant? Why?

Much of what we know about gene interactions in development has been learned using nematodes, yeast, flies, and bacteria. This is due, in part, to the relative ease of genetic manipulation of these well-characterized genomes. However, of great interest are gene interactions involving complex diseases in humans. Wang and White [(2011). Nature Methods 8(4):341–346] describe work using RNAi to examine the interactive proteome in mammalian cells. They mention that knockdown inefficiencies and off-target effects of introduced RNAi species are areas that need particular improvement if the methodology is to be fruitful.

How might one use RNAi to study developmental pathways?

Dominguez et al. (2004) suggest that by studying genes that determine growth and tissue specification in the eye of Drosophila, much can be learned about human eye development.

What evidence indicates that the eyeless gene is part of a developmental network?

Vulval development in C. elegans is dependent on the response of some of the central epidermal progenitor cells in the region of the developing vulva to a chemical signal from the gonad. Signaling from the gonad is blocked by action of the vulvaless mutant let-23 so that none of the central progenitor cells form vulval structures. In the vulvaless mutant, n300, the central progenitor cells do not form.

Which gene is likely to act earlier in the vulval developmental pathway?

Dominguez et al. (2004) suggest that by studying genes that determine growth and tissue specification in the eye of Drosophila, much can be learned about human eye development.

What evidence suggests that genetic eye determinants in Drosophila are also found in humans? Include a discussion of orthologous genes in your answer.