The molecular basis for the cerebellar anomalies seen in Joubert syndrome patients is unknown and is likely genetically distinct from classical Joubert syndrome. Mutations in genes that regulate early specification and development of domains of the cerebellum may be responsible for the brain abnormalities observed in Joubert syndrome. The early specification of cerebellar territory in vertebrates is regulated via the expression of homeotic genes. These homeotic genes are homologous to the segment-polarity genes in Drosophila, which encode transcription factors known as "paired-box," or Pax genes. Their transcripts influence the expression of vertebrate homologues of engrailed (en), a Drosophila gene encoding a transcription factor containing a homeobox domain. The expression of en genes is further regulated by wnt1, a homologue of the Drosophila wingless gene. The wnt1 gene is primarily expressed during early neuronal development. Disruption of wnt1 results in agenesis of cerebellar structures. Recently, the wnt1 gene has been excluded as being causative for Joubert syndrome.