Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents ~30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe the first zebrafish model of SHH MB using CRISPR to mutate ptch1, the primary genetic driver in human SHH MB. These tumors rapidly arise adjacent to the valvula cerebelli and resemble human SHH MB by histology and comparative genomics. In addition, ptch1-deficient MB tumors with loss of tp53 have aggressive tumor histology and significantly worse survival outcomes, comparable to human patients. The simplicity and scalability of the ptch1 MB model makes it highly amenable to CRISPR-based genome editing screens to identify genes required for SHH MB tumor formation in vivo, and here we identify the grk3 kinase as one such target.

Comparing the relative volumes of body parts is a useful tool in morphology, but it is not trivial to do this in animals that differ in overall size. To account for scaling differences, a \"reference size\" has to be determined and the original absolute volumes have to be \"corrected for\" by this scaling reference. However, the outcome of a statistical analysis is greatly affected by this \"reference size,\" and it is practically impossible to determine the \"overall size\" of a structure independent of the changes in the relative size of the parts of it. Here, a new method is introduced to compare the relative volumes of parts that does not need a scaling reference. The method transforms the absolute part volumes into a ratio matrix (volume ratio transformation, VRT). The VRT is free of any scaling factors and can be used to compare groups of animals. This paper also reviews various other errors made frequently when comparing brain morphology between animals. Finally, the VRT is applied to investigate sex differences in the swordtail fish (Xiphophorus hellerii), which show profound differences in the size of the valvula cerebelli.

This study is a re-examination of the direct primary sensory input to the valvula cerebelli in spiny eel. The valvula in Macrognathus zebrinus receives a primary afferent projection from the trigeminal nerve as revealed by injections of biotinylated dextran amines into the rostrum. The descending trigeminal nucleus and nucleus of the tractus solitarius are innervated as well. Injections with DiI into the valvula labeled fibers in the descending trigeminal nucleus. The projection of tactile information from the rostrum to the valvula may be an adaptation of food search for spiny eels in regard to their highly mobile rostrum.