FGD1 as a central regulator of extracellular matrix remodelling--lessons from faciogenital dysplasia

J Cell Sci. 2012 Jul 15;125(Pt 14):3265-70. doi: 10.1242/jcs.093419. Epub 2012 Aug 1.


Disabling mutations in the FGD1 gene cause faciogenital dysplasia (also known as Aarskog-Scott syndrome), a human X-linked developmental disorder that results in disproportionately short stature, facial, skeletal and urogenital anomalies, and in a number of cases, mild mental retardation. FGD1 encodes the guanine nucleotide exchange factor FGD1, which is specific for the Rho GTPase cell division cycle 42 (CDC42). CDC42 controls cytoskeleton-dependent membrane rearrangements, transcriptional activation, secretory membrane trafficking, G1 transition during the cell cycle and tumorigenic transformation. The cellular mechanisms by which FGD1 mutations lead to the hallmark skeletal deformations of faciogenital dysplasia remain unclear, but the pathology of the disease, as well as some recent discoveries, clearly show that the protein is involved in the regulation of bone development. Two recent studies unveiled new potential functions of FGD1, in particular, its involvement in the regulation of the formation and function of invadopodia and podosomes, which are cellular structures devoted to degradation of the extracellular matrix in tumour and endothelial cells. Here, we discuss the hypothesis that FGD1 might be an important regulator of events controlling extracellular matrix remodelling and possibly cell invasion in physiological and pathological settings. Additionally, we focus on how studying the cell biology of FGD1 might help us to connect the dots that link CDC42 signalling with remodelling of the extracellular matrix (ECM) in physiology and complex diseases, while, at the same time, furthering our understanding of the pathogenesis of faciogenital dysplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dwarfism / genetics*
  • Dwarfism / metabolism
  • Extracellular Matrix / genetics*
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Face / abnormalities
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / metabolism
  • Genitalia, Male / abnormalities
  • Genitalia, Male / metabolism
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / metabolism
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / metabolism
  • Humans
  • cdc42 GTP-Binding Protein / metabolism


  • FGD1 protein, human
  • Guanine Nucleotide Exchange Factors
  • cdc42 GTP-Binding Protein

Supplementary concepts

  • Aarskog Syndrome