Dr. Randy L. Johnson
The University of Texas MD Anderson Cancer Center
Department of Biochemistry and Molecular Biology
- Mouse genetics
- Pattern formation
- Gene targeting
Research in my laboratory focuses on genetic regulation of vertebrate pattern formation, with emphasis on key regulators of dorsal-ventral limb, somite, and eye development. Highlights of recent studies include the characterization of lmx1b-mutant mice that exhibit a striking ventral-to-dorsal limb transformation. Additionally, we have determined that a congenital human disease, nail-patella syndrome, is caused by mutations in the LMX1B gene. Part of the nail-patella phenotype is glaucoma, and we are using our lmx1b-mutant mice to gain further insight into the mechanisms underlying congenital glaucomas in humans.
We have obtained another significant finding by generating and characterizing mice with mutations in the lunatic fringe gene. These mutants exhibit a striking disordering of their axial skeleton, pointing toward Lunatic fringe as a key regulator of the segmentation process in vertebrates. Present efforts to understand the segmentation mechanisms include functional characterization of novel families of transcription factors expressed in the presomitic mesoderm. Until now, our major experimental approach has been to generate mutant alleles via gene targeting in murine embryonic stem cells. In future studies, we will complement this approach with transgenic analysis to define novel genetic cascades in limb, somite, and eye development and with forward-genetic studies to identify novel genes with essential roles in these processes.
A tutorial in my laboratory would provide experience in molecular biology, in situ hybridization, tissue culture, gene targeting in the mouse, and experimental embryology of the chick.
Program in Genes and Development