The tetrapod skull is a vastly diverse structure due to complex interacting factors including phylogeny and development. In amniotes, it is known that brain expansion has influenced skull evolution wherein cranial vault expansion correlates with cerebral hemisphere expansion. However, the molecular basis for this correlation, and whether such a correlation exists in non-amniotes, has not been solidified. Previous research has proposed that the resulting skull bones are spatially related to the embryonic brain at its 3-vesicle stage, with the frontal bone developing in tandem with the forebrain. To understand the interaction at a molecular level, our research aims to conduct knockdown experiments for key regulatory genes of forebrain development in Xenopus laevis and Ambystoma mexicanum. These two species were chosen for their differing cranial proportions (i.e. X. laevis has a shorter frontal [part of the frontoparietal], whereas A. mexicanum has a longer frontal) and for their potentially correlated proportions of the developing brain. Our hypothesis is that if key forebrain regulatory genes are inhibited during early developmental stages, then the resulting frontal bone development should also be affected, confirming a gene level interaction. In addition, we will conduct forebrain transplants between the two species before the forebrain tissue becomes committed to its developmental fate. If the forebrain tissue is communicating directly with the skull, then the resulting skull should resemble that of the transplanted species. These results will yield novel data on amphibian brain developmental genetics as well as revealing an underexplored aspect of tetrapod skull evolution – the brain.