On the emergence of folding in the cerebellum

The gross structure of the human cerebellum is divided into an intricate pattern of lobules by fissures that extend across the surface. The folded shape, and its emergence during development, presents an exciting problem of tissue morphogenesis. While other structures in the human brain are folded, the cerebellum is a tractable model for studying neural tissue folding. The cerebellum folds in small, inexpensive model systems including the mouse where there is a wealth of descriptive and mutational data. Computational models have also been developed to predict how cerebellar folding may be regulated, generating testable hypotheses. The relatively simple folding pattern of the murine cerebellum, and the well-established genetic tools provide an exciting opportunity to challenge hypotheses and to dissect the underlying regulation that controls the amount and pattern of folding. In this chapter a descriptive analysis of the folding of the murine cerebellum is given. A modeling framework for understanding the mechanics of folding, explicit to the cerebellum, is discussed in terms of the developmental data. Then several categories of folding phenotypes, from various perturbations, are discussed in terms of the modeling and the cell and tissue-level mechanics predicted to be involved. Finally, the chapter concludes with brief comments about the future directions of the field.