Foxc1 is required for early stage telencephalic vascular development.
BACKGROUND
The brain vascular system arises from the perineural vascular plexus (PNVP) which sprouts radially into the neuroepithelium and subsequently branches off laterally to form a secondary plexus in the subventricular zone (SVZ), the subventricular vascular plexus (SVP). The process of SVP formation remains to be fully elucidated. We investigated the role of Foxc1 in early stage vascular formation in the ventral telencephalon.


RESULTS
The Foxc1 loss of function mutant mouse, Foxc1(ch/ch) , showed enlarged telencephalon and hemorrhaging in the ventral telencephalon by embryonic day 11.0. The mutant demonstrated blood vessel dilation and aggregation of endothelial cells in the SVZ after the invasion of endothelial cells through the radial path, which lead to failure of SVP formation. During this early stage of vascular development, Foxc1 was expressed in endothelial cells and pericytes, as well as in cranial mesenchyme surrounding the neural tube. Correspondingly, abnormal deposition pattern of basement membrane proteins around the vessels and increased strong Vegfr2 staining dots were found in the aggregation sites.


CONCLUSIONS
These observations reveal an essential role for Foxc1 in the early stage of vascular formation in the telencephalon.
Section of Molecular Craniofacial Embryology, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.
Thanit
T
Prasitsak
Mya
M
Nandar
Shigeru
S
Okuhara
Shizuko
S
Ichinose
Masato S
MS
Ota
Sachiko
S
Iseki
D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000098:blood supply / Q000196:embryology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D013687:Telencephalon / Q000098:blood supply / Q000196:embryology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics
D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
Foxc1; angiogenesis; basement membrane; subventricular vascular plexus; telencephalon