ZIC2 and holoprosencephaly: We have chosen Zic2 for this proof-of-concept study firstly, because existing targeted models have only resulted in reduced Zic2 expression [31], secondly, because heterozygous Zic2 loss-of-function results in a visible phenotype, albeit with variable penetrance [34] and thirdly, as the TALEN mutagenesis approach has the potential to generate an allelic series of mutations which, when targeted to the functional zinc finger domain of this transcription factor, could model many of the human mutations associated with holoprosencephaly [33].