The gene PAX6 is located on chromosome 11 (1 lpl3) and encodes a transcription factor (PAX6)
that is expressed early in development. The PAX6 protein is expressed in the developing eye,
regions of the brain, central nervous system (CNS), nasal epithelium and pancreas. PAX6 is best
known for its role in eye development with heterozygous mutations causing congenital ocular
malformations. However, it must be remembered that PAX6 has multiple functions in the brain
including specification of neuronal subtypes and axon guidance.
There is growing understanding of the role of PAX6 as a transcription factor during
development, and many of its DNA targets have recently been defined. However, almost nothing
is known about the proteins with which PAX6 interacts.
In the initial stage of my research I identified a conserved region consisting of the final 32 amino
acids of the PST (proline, serine and threonine rich) domain of PAX6. Based on sequence
homology and secondary structure predictions I classed this region as a novel domain, the 'C
terminal domain'. Next I used the yeast 2-hybrid system to investigate possible PAX6 protein
interactions. By screening a mouse brain cDNA library with the C terminal domain and whole
PST domain, I identified three novel and interesting interactors, Homer3, Dncll and Triml 1.
I re-confirmed these interactions in a pairwise manner using the yeast 2-hybrid system, and I
showed that the C terminal domain was vital for the interactions between PAX6 and Homer3 or
Dncll. Furthermore, certain C terminal mutations that are known to cause ocular malformations
in patients are also sufficient to reduce or abolish these interactions. I attempted to further
characterise the interactions by co-immunoprecipitation. However, this was not possible due to
Although speculative at present, the finding that PAX6 may interact with Homer3 (a component
of the post synaptic density) and Dncll (a subunit of the motor protein dynein) alludes to an
interesting new role for PAX6 in neurogenesis.