Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain.
Prevailing notions of cerebral vascularization imply that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations. Endothelial cells, building blocks of blood vessels, are thought to be homogeneous in the brain with respect to their origins, gene expression patterns and developmental mechanisms. These current notions that cerebral angiogenesis is regulated by local environmental signals contrast with current models of cell-autonomous regulation of neuronal development. Here we demonstrate that telencephalic angiogenesis in mice progresses in an orderly, ventral-to-dorsal gradient regulated by compartment-specific homeobox transcription factors. Our data offer new perspectives on intrinsic regulation of angiogenesis in the embryonic telencephalon, call for a revision of the current models of telencephalic angiogenesis and support novel roles for endothelial cells in brain development.
Vasudevan
Anju
A
Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA. anju.vasudevan@mgh.harvard.edu
Long
Jason E
JE
Crandall
James E
JE
Rubenstein
John L R
JL
Bhide
Pradeep G
PG
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000196:embryology* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013687:Telencephalon / Q000098:blood supply* / Q000196:embryology*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D042787:Receptor, TIE-2