The tetrapod skull has evolved in response to various pressures over its long evolutionary history. One such pressure is the expansion of the cerebral hemispheres of the brain, which has been shown to drive physical changes in the craniofacial skeleton in certain lineages. The molecular basis of these brain-skull interactions remains incompletely understood, though studies indicate that key to this relationship is the range of morphogenetic signals originating from signaling sources within the forebrain. Knockdown experiments in mouse and chick have been conducted to eliminate these signals and study the resulting morphology; however, interrupting gene expression may have off-target effects. An alternative method of eliminating local signals is tissue removal/ablation. To better understand the role of the forebrain in shaping cranial development, forebrain removal experiments were conducted in Xenopus laevis, a representative of the poorly studied amphibians, to study the resulting morphology of the skull. To facilitate these comparisons, a detailed internal staging guide for X. laevis was developed, expanding on the widely used Nieuwkoop and Faber series. Next, it was found that removal of forebrain tissue in early tailbud embryos resulted in craniofacial deformities, as well as a disruption of olfactory and optic sensory development. Potential biochemical causes of these results are discussed within the context of knowledge from amniote systems. These findings indicate that the role of the forebrain in craniofacial development seen in amniotes is likely conserved in X. laevis, providing vital information for our understanding of tetrapod skull evolution.
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