Randy L. Johnson

Vertebrate pattern formation

Research in our laboratory centers 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 mutant lmx1b alleles in mice to gain further insight into the mechanisms underlying congenital glaucomas in humans. Another significant finding was obtained from the generation and characterization of lunatic fringe mutants. These mutants exhibit a striking disordering of the axial skeleton and point towards lunatic fringe as a key regulator of the segmentation process in vertebrates. Present efforts to understand the segmentation mechanisms in our laboratory include functional characterization of novel families of transcription factors expressed in the presomitic mesoderm. Up to now, our major experimental approach has been to generate mutant alleles via gene targeting in murine embryonic stem cells. In future studies, we plan to compliment this approach with transgenic analysis to define novel genetic cascades in limb, somite, and eye development and forward genetic studies to identify novel genes with essential roles in these processes.

Selected Publications

Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, Johnson RL, Lee B (1998) Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nature Genetics 19:47-50.

Chen H, Lun Y, Ovchinnikov D, Kokubo H, Oberg KC, Pepicelli CV, Gan L, Lee B, Johnson RL (1998) Limb and kidney defects in lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nature Genetics 19:51-55.

Evrard YA, Lun Y, Aulehla A, Gan L, Johnson RL (1998) lunatic fringe is an essential mediator of somite segmentation and patterning. Nature 394:377-381.

Aulehla A, Johnson RL (1999) Dynamic expression of lunatic fringe suggests a link between notch signaling and an autonomous cellular oscillator driving somite segmentation. Developmental Biology 207:49-61.

Lu MF, Pressman C, Dyer R, Johnson RL, Martin JF (1999) The function of the Rieger syndrome gene, Pitx2, in left-right morphogenesis and craniofacial development. Nature 401:276-278.

Pressman CL, Chen H, Johnson RL (2000) LMX1B, a LIM homeodomain class transcription factor, is necessary for normal development of multiple tissues in the anterior segment of the murine eye. Genesis 26:15-25.

Smidt MP, Asbreuk CH, Cox JJ, Chen H, Johnson RL, Burbach JP (2000) A second independent pathway for development of mesencephalic dopaminergic neurons requires Lmx1b. Nature Neuroscience 3:337-341.

Chen H, Johnson RL (2002) Interactions between dorsal-ventral patterning genes lmx1b, engrailed-1 and wnt-7a in the vertebrate limb. International Journal of Developmental Biology 46:937-941.

Contact Information

Randy L. Johnson, Ph.D.

Department of Biochemistry and Molecular Biology

The University of Texas

M.D. Anderson Cancer Center

1515 Holcombe Boulevard, S11.8136B

Houston, Texas 77030, U.S.A.

Tel: (713) 834-6287

Fax: (713) 834-6291

E-mail: rljohnso@mdanderson.org