Characterization of the overlapping expression patterns of the zebrafish LIS1 orthologs

Abstract

Mutations in the LIS1 ( Lissencephaly-1) gene underlie classical lissencephaly. This neurodevelopmental disorder is characterized by a loss of cortical gyri and improper laminar formation of the brain due to impaired neuronal migration. Patients with type 1 lissecephaly present with mental retardation and an increased risk of developing other disorders resulting from abnormal neurodevelopment, such as epilepsy. LIS1 is a dynamic protein implicated in numerous cellular mechanisms important for brain development. We have cloned and characterized the orthologs of LIS1 in the zebrafish. The zebrafish is a well-documented model organism for studies of brain development and offers many advantages including embryonic transparency, the ability to easily manipulate gene expression and also generate transgenic animals which can be used to track single, migrating neurons. In the zebrafish nervous system, the LIS1 orthologs are expressed in overlapping temporal and partially overlapping spatial patterns. While lis1a is primarily expressed in the developing central nervous system and the eye, lis1b is highly expressed in the peripheral nervous system as well as the Rohon-beard neurons. Rohon-beard neurons are the early sensory system of the embryo. We postulate that understanding the functions of Lis1 in the whole embryo will provide better insight into the genetic and neurodevelopmental basis of lissencephaly. This will not only aid in the development of therapeutic interventions for diseases such as lissencephaly but will also contribute to the general understanding of brain development.