The short stature homeobox gene SHOX

SHOX

Short stature is a growth disorder with often unknown genetic causes. Defects in early developmental genes may be responsible for this kind of growth disorder.

The most frequent cause of idiopathic short stature up to date concerns the SHOX gene that we isolated and characterized in our department. Gene defects of the homeobox transcription factor SHOX can be found in syndromal (Léri- Weill, Langer and Turner syndrome) and nonsyndromal
(idiopathic) short stature. At the present time we are analyzing different cell systems and animal models (mouse, frog, chicken) to better understand the function of SHOX during bone development and the exploitation of the molecular signal pathway. The characterization of regulatory processes as well as the identification of different target genes activated by SHOX through si-RNA,microarray and ChIP methods, are topics of thorough research. They are supposed to help us understand the SHOX-dependent early developmental biological processes.

SHOX2

SHOX and SHOX2 are highly homologous genes that belong to a small group of homeobox transcription factors with essential functions during early embryogenesis, especially in limb, heart and brain development. By  combining different animal models (transgenic and knock-out mice, frog, zebrafish and chick) as well as cell culture systems (mouse embryonic stem cells, primary chondrocytes and fibroblasts) we investigate the role of SHOX2 during different developmental processes.Insights from our work with the Shox2 knockout mouse model may contribute to the current understanding of cardiac arrhythmia.

In addition, we aim to identify and further characterise the SHOX2-dependent signalling cascades by using cellular, molecular and biochemical approaches. Based on the high homology to SHOX, we are particularly interested in similarities, interactions and redundant functions of the two transcription factors as well as differences driven by highly specific factors and regulatory mechanisms during early development.