Regulation and function of homeodomain proteins in the embryonic and adult vascular systems.
During embryonic development, the cardiovascular system first forms and then gives rise to the lymphatic vascular system. Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. These genes all encode proteins that are transcription factors that contain a well conserved DNA binding motif, the homeodomain. It is through the homeodomain that these transcription factors bind to the promoters of target genes and regulate their expression. Although many homeodomain proteins have been found to be expressed within the vascular systems, little is known about their downstream target genes. This review highlights recent advances made in the identification of novel genes downstream of the homeodomain proteins that are necessary for regulating vascular cellular processes such as proliferation, migration, and endothelial tube formation. Factors known to regulate the functions of vascular cells via modulating the expression of homeobox genes will be discussed. We will also review current methods used to identify and characterize downstream target genes of homeodomain proteins.
Douville
Josette M
JM
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
Wigle
Jeffrey T
JT
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D042583:Lymphangiogenesis / Q000235:genetics; D042601:Lymphatic Vessels / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000098551:Prospero-Related Homeobox 1 Protein
C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; C484194:Meox2 protein, mouse; C489936:Prrx1 protein, mouse; C115469:Prrx2 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C088144:HoxA protein