Hello,

I am Emilia Pavel, graduate research associate in Dr. Lawrence Kirschner’s laboratory, in the Department of Molecular Virology, Immunology, and Molecular Genetics, at the Ohio State University in Columbus, Ohio.
In the next few minutes I will make a short introduction of our paper entitled: “Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region” which appeared in “International Journal of Developmental Biology” 2007.

The formation of the vertebrate limb illustrates an important paradigm in development, as it involves distinct transcriptional and signaling programs along each of the three axes, proximal-distal, dorsal-ventral, and anterior-posterior.

Interesting aspects of this process have been revealed by studying the limb deformity (ld) phenotype.
This phenotype is characterized by foreshortening of the distal appendages, both upper and lower, including fusion of distal limb bones and malformation of the paws.

It is known that this phenotype is caused by loss of the BMP-antagonist Gremlin in the limb buds, either through mutation of Grem1, or by loss of a transcriptional global control region (GCR) located in the neighboring Fmn1 gene.

In this report, we present a new allele of ld, which is the limb deformity phenotype,and show that this allele is, in fact, a deletion of the entire Fmn1 gene,including its GCR.

In order to understand the effects of loss of the Ld GCR, we have tested the expression of Gremlin1 in other tissues, as well as studied the effects of this mutation on the expression of neighboring genes.

These data reveal that the major role of the Ld GCR is to regulate the expression of the Grem1 gene in the developing limb, although it also exerts subtle effects on other genes within this chromosomal environment.