- 2005. Columbia University. PhD.
- Stochastic events play an important role in many biological processes. The p and y ommatidial subtypes are distributed stochastically in the retina, similarly to human cone PR distribution. R7s first make the p vs. y choice and then impose fate onto R8. The stochastic expression of the spineless gene in R7 determines which ommatidia become p or y. Whereas most stochastic systems are controlled by random activation, stochastic spineless expression is determined by global activation coupled with random repression requiring combinatorial inputs from multiple cis-regulatory elements acting at long range. A transvection-like mechanism coordinates expression of the two spineless alleles to yield a robust frequency of expression. Spineless induces expression of Rh4, repression of Rh3, and inhibition of a signal to R8s. It directly activates the rh4 promoter, whereas it triggers a complex interlocked feedforward loop motif to indirectly repress rh3. These distinct modes of regulation determine differential response thresholds to stochastic Spineless activity. Therefore, this stochastic system is finely tuned to trigger distinct network motifs that determine stochastic or regional expression outcomes by overriding or incorporating underlying biases.
- Jane Coffin Childs Memorial Fund