Developmental Neurobiology & Genomics Laboratory

Lab head: Thomas Becker












Analysis of genes involved in X-linked neurological diseases using the genetic model system zebrafish

Primary supervisor: Silke Rinkwitz

As part of an international consortium, our lab focuses on the genetic basis underlying X-linked neurological diseases. Current estimates suggest close to 100 loci causing X-linked intellectual disability (XLID), as well as numerous loci involved in demyelinating diseases, epilepsy, autism and spastic paraplegia and some eye anomalies. Because of their relatively high prevalence and their social importance, the genetic defects underlying XLID are actively pursued at many levels. Severe XLID is often caused by chromosomal aberrations or defects in specific genes, while milder forms are thought to result from interaction of multiple genes and environmental factors.

Since the gross brain anatomy and the neurotransmitter systems as well as the genetic mechanisms in brain development are well conserved between human and zebrafish, we use the zebrafish as a model system to analyze the function and regulation of disease genes. An external, rapid development, transparent embryos and a sequenced genome established this model especially for the genetic study of developmental processes and diseases.

We use transgenic approaches for analyzing X-linked neurological disease genes. We create zebrafish lines with genomic modifications that can be used to reveal the sites of activity of the gene of interest and also, for functional analyses, to modify the activity of the gene in living embryos/larvae.

The project aims to characterize the fluorescent expression pattern of a transgenic zebrafish line expressing a reporter under regulatory control of a XLID gene to indicate its expression sites in the developing brain. The findings will be related to the human brain to get indications of disease causing mechanism in intellectually disabled patients. This work required breeding of fish, egg collection, staging/handling of larvae, immunohistochemial procedures (antibody stainings), tissue sectioning and microscopy. The student should have interest in brain anatomical studies, brain development and brain diseases.

Discipline: Anatomy & Histology
Co-supervisors: Tom Becker
Keywords: Genetic diseases, Brain, developmental neurobiology
Contact: Email Silke Rinkwitz