Vascular morphogenesis: tales of two syndromes

Autor: Sudha Srinivasan, Jon S. Zawistowski, Douglas A. Marchuk, Teresa L. Squire
Rok vydání: 2003
Předmět:
Cell signaling
Integrins
Cellular differentiation
Activin Receptors
Type II
Amino Acid Motifs
Morphogenesis
Vascular Cell Adhesion Molecule-1
Receptors
Cell Surface
Cell Communication
Biology
medicine.disease_cause
Models
Biological
Vascular anomaly
Mice
Antigens
CD
Transforming Growth Factor beta
Proto-Oncogene Proteins
Genetics
medicine
Cell Adhesion
Animals
Humans
Molecular Biology
KRIT1 Protein
Genetics (clinical)
Cytoskeleton
Genes
Dominant
Regulation of gene expression
Mice
Knockout
Mutation
Brain Diseases
Neovascularization
Pathologic
Genetic disorder
Endoglin
Arteriovenous malformation
General Medicine
Syndrome
medicine.disease
Protein Structure
Tertiary
Blood Vessels
Telangiectasia
Hereditary Hemorrhagic
Activin Receptors
Type I
Microtubule-Associated Proteins
Cell Division
Signal Transduction
Zdroj: Human molecular genetics.
ISSN: 0964-6906
Popis: Advances in our understanding of fundamental biological processes can be made by the analysis of defects manifested in inherited diseases. The genes responsible for these genetic syndromes often encode proteins that act at critical points of the pathways that control biological processes such as cell proliferation, cell-cell communication, cellular differentiation, and cell death. This approach has lead to the discovery of novel gene products and/or biochemical pathways involved in disease, genes that in turn play a fundamental role in normal biological processes. This forward genetic approach, focusing on Mendelian disorders of vascular anomalies, has been particularly fruitful for the study of genetic regulation of angiogenesis. This review summarizes the ongoing saga of two genetic syndromes involving disruption of normal vascular morphogenesis. Each inherited disorder involves the focal development of a distinct vascular anomaly. In hereditary hemorrhagic telangiectasia (HHT), the hallmark vascular lesion is termed an arteriovenous malformation, which involves the direct communication of an artery with a vein (arteriovenous shunt), without an intervening capillary bed. For cerebral cavernous malformations (CCM), the lesions are grossly-dilated, closely-packed, capillary-like sinusoidal chambers. The autosomal dominant mode of inheritance of each of these distinct syndromes suggested that the underlying genes might regulate critical aspects of vascular morphogenesis. Emerging but intriguing tales are being told by the genes (and their protein products) mutated in these disorders.
Databáze: OpenAIRE
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