The Mortlock laboratory studies the regulation and evolution of several genes involved in vertebrate skeletal development. These projects will help shed light on the gene regulatory events driving skeletal bone and cartilage formation, and the structure of genomic sequences affecting gene regulation. This is relevant to human afflictions ranging from birth defects to arthritis and osteoporosis. In addition we are extensively using cross-species genome sequence comparisons to locate cis-regulatory elements. Currently, the Morltock lab is studying 3 members of the BMP (Bone Morphogenetic Protein) gene family: Gdf6, Bmp2 and Bmp4. All are transcribed in complex patterns during vertebrate development. Precise regulation of these genes is likely controlled by multiple cis-regulatory elements, which can be located through transgenic analysis. All three genes are flanked by large "gene deserts" that contain strongly conserved noncoding sequences. It is likely that the modification of regulatory sequence has enabled evolution of diverse skeletal morphologies, so the mapping and function of these sequences is of great interest. Using mice and/or zebrafish to perform BAC and plasmid transgene reporter assays, lab members are mapping numerous long-range conserved sequences flanking each gene.

RECENT PUBLICATIONS

Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis.  2009 Genes & Immunity 23 July

Regenerative effects of transplanted mesenchymal stem cells in fracture healing.  2009 Stem Cells 27: 1887-1898

Identification of an ancient Bmp4 mesoderm enhancer located 46 kb from the promoter.2009 Developmental Biology 327: 590-602

Fate mapping using Cited 1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia.  2008 Developmental Biology 313: 234-245