The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain Heather C. Etchevers, Christine Vincent, Nicole M. Le Douarin and Gerard F. Couly
Development 128, 1059-1068 (2001)
Development 128, 1059-1068 (2001)
Большая часть соединительной ткани головы формируется клетками neural crest (NCCs), популяцией эмбриональных клеток, присутствующей только у позвоночных. Производные NCC перициты и гладкомышечные клетки распределены в четко определенном секторе сети сосудов (vasculature) у эмбрионов птиц. Т.к. NCCs отсоединяются от нейральных складок, которые соответствуют будущим задней части диэнцефалона, мезэнцефалону и ромбэнцефалону, то они мигрируют между эктодермой и нейроэпителием в передне/вентральную часть головы, встречаясь там с эндотелиальными предшественниками, производными мезодермы. Вместе эти две популяции клеток строят сосудистое древо, корнем которого является аорта, исходящая из сердца, и которое разветвляется на капиллярные сплетения, которые омывают менингиальные оболочки переднего мозга, снабжают ретинальное хороидное сплетение и все лицевые структуры, прежде чем вернуться в сердце. NCCs входят состав стенок каждого сосуда, происходящего из аортальных дуг, обеспечивая каждый компонент, за исключением эндотелиальных клеток. Внутри менингиальных оболочек, капиляры с перицитами, происходящими из diencephalic и
mesencephalic нейральных складок питают передний мозг, тогда как капиляры с перицитами мезодермального происхождения питают остальную часть ЦНС взаимоисключающим способом. Два типа головной vasculature контактируют в небольшом количесстве строго определенных мест, включая анастомозирующие сосуды в кольце Willis, непосредственно вентральнее границы между передним и средним мозгом. В ходе эволюции, subphylum позвоночыных м. эксплуатировать в чрезвычайно широких пределах онтогенетический потенциал и пластичность NCCs в голове, ремоделируя то, что привело в результате к росту переднего мозга.
(Рис.1) The dorsal cephalic vascular tree, excluding the jaws, ventral view. Six pairs of aortic arch arteries form during amniote embryogenesis, looping from the ventral to the dorsal aorta. Three of them persist in the adult: the third pair, as a segment of the common carotid arteries; one of the fourth pair, as the aorta; and the sixth, as a segment of the pulmonary arteries. The common carotid arteries give rise to a ventral arterial pathway, of which the internal carotid (C. i.) and derived arteries (pink) target the upper face, eyes, and forebrain. The distal part of this route is made of vascular elements derived from the first three aortic arches. The other arterial pathway in the head (green) targets the midbrain and hindbrain, and arises from the vertebral arteries (V.). Both trees start from the brachiocephalic artery trunks, which diverge from the ventral (ascending) aorta. The common carotid arteries immediately course into the neck and face. The vertebral arteries project into the head along the underside of the hindbrain after fusing to form the basilar artery. The two systems contact at the circle of Willis (box), which surrounds the optic chiasm ventral to the diencephalon. The posterior sides of this famous vascular polygon are made by the bifurcation of the basilar artery,while derivative branches of the internal carotid arteries constitute the anterior sides. An anastomotic artery, the posterior communicante (P. c.), connects them; in humans, a median fusion between the anterior cerebral arteries completes the ‘circle’. The circle of Willis represents the anatomical interface between the ventral and dorsal vascular trees. B., basilaris; C. c. a., carotis cerebralis anterior; C. c. m., carotis cerebralis medialis; C. c. p., carotis cerebralis posterior; Ce. d., cerebellaris dorsalis; Ce. v., cerebellaris ventralis;C. i., carotis interna; Eth., ethmoidalis; T. m. d., tecti mesencephalis dorsalis; T. m. v., tecti mesencephalis ventralis; V, vertebralis. Adapted, with permission, from Baumel (Baumel, 1979).
(Рис.2) Cephalic NCCs and mesodermal cells intermingle by way of opposing dispersion patterns. (A) Section through a HH7 (4ss, early E2) embryo at level of the presumptive diencephalon. No mesodermal cells, in particular endothelial precursors (blue, Vegfr2 expression), intervene between the ectoderm and the prosencephalic alar plate. (B) Distribution of rostral-spreading NCC (red, Sox10 expression) and endothelial cells (blue, Vegfr2 expression) at early HH10 (10ss, E2) in a transverse section at the level of the anterior prosencephalon. (C) Parasagittal section of HH14 (E2) embryo, anterior right. Endothelial cells (blue, Vegfr2 expression) and NCCs (red, Sox10 expression) occupy the mesenchyme intervening between the neuroepithelium and ectoderm except around the rostral telencephalon. Sox10 is also expressed in the ventral diencephalon (see Cheng et al., 2000). Boxed region is magnified in D. (D) NCCs precede endothelial tubes as they insinuate together between the ectoderm and neuroepithelium of the telencephalon. (E) Distribution of NCCs (brown, QCPN IHC) at HH14 after a unilateral graft of an anterior mesencephalic neural fold, in transverse section at the level of the ventral diencephalon. NCCs disperse bilaterally rostral to the graft but remain unilateral near the pharynx. (F) On a slightly more anterior section of the same embryo, grafted NCCs can be seen to separate neuroepithelium from ectoderm and to be accompanied by capillaries (asterisk) as in D. (G) NCCs (arrows) from a grafted mesencephalic neural fold begin to penetrate the telencephalic neuroepithelium from the surrounding mesenchyme at HH24 (E4). Scale bars: 100 mm in A-C,E,G: 50 mm in D,F.
(Рис.3) NCCs associated with blood vessels in the head are pericytes or smooth muscle cells. (A) Slightly oblique transverse section of an embryo grafted with an anterior mesencephalic neural fold at HH32 (E8). Quail cells are visualised with QCPN IHC in blue; a smooth muscle actin IHC is in brown. Note that blue NCCs are concentrated around the forebrain, in contrast to the rest of the central nervous system. Regions magnified in B and C are indicated. (B) Telencephalic meninges are full of quail cells, some of which penetrate the neuroepithelium and co-localise with a smooth muscle actin. (C) The double labelling of grafted cells with a smooth muscle actin within the internal carotid artery tunica media indicates that these NCCs have become smooth muscle cells (arrows). (D) Similar double-labelling within the neuroepithelial capillaries shows NCC-derived pericytes (arrows); unlabelled endothelial cells are indicated with arrowheads. Scale bars: 1 mm in A; 50 mm in B,C; 100 mm in D.
(Рис.4) Sequential distribution of NCC from successive neural fold origins in the walls of cephalic arteries. (A) Cephalic NCCs (colours, this study) and mesoderm (greys; Le Liиvre, 1976; Couly et al., 1987) contribute to the musculo-connective wall of separate arterial trees in the head. Red corresponds to cells derived from posterior diencephalic (PD), anterior and posterior mesencephalic (AM, PM) neural folds; orange corresponds to rhombomere (r)1; yellow to r2; green to r4; turquoise to r5; and blue to r6 (in the vascular media of a schematic E7.5 chicken head). Boundaries overlap between domains ensured by NCCs of given origins in vessel walls. Within the meninges of the central nervous system, pink denotes those derived from PD, AM and PM NCCs; grey denotes those of mesodermal origin, with a sharp boundary between the two at the diencephalon/mesencephalon junction. Levels of sections shown in C-F are indicated, where lower panel is a magnification of the artery indicated in the upper panel. Levels of Fig. 3B and 3C are also shown. (B) Ink-injected E8 quail, showing both branchial and vertebral artery ramifications. (C-F) The lower panels show the enlargement of the areas boxed in the upper panels. (C) E8 chimera after graft of PD neural fold, in transverse section – internal carotid artery. (D) E8 chimera after graft of r2 neural fold, in transverse section – maxillary artery. (E) E8 chimera after graft of r4 neural fold, in transverse section – stapedian artery. Quail cells revealed by Feulgen-Rossenbeck stain (lower panel inset) are false-coloured in brown in the lower panel. (F) E8 chimera after graft of r5 neural fold, in transverse section – common carotid artery. B., basilaris; C. c. a., carotis cerebralis anterior; C. c. m., carotis cerebralis medialis; C. c. p., carotis cerebralis posterior; Ce. v.,cerebellaris ventralis; C. i., carotis interna; Eth., ethmoidalis; L., lingualis; Md., mandibularis; Mx., maxillaris; Occ., occipitalis; Oph.,ophthalmica interna; P. c., posterior communicante (circle of Willis); St., stapedia; St. te., stapedia temporalis; St. sup., stapedia supraorbitalis; T. m. v., tecti mesencephalis ventralis; V, vertebralis. Adapted, with permission, from Hughes (Hughes, 1934) and Baumel (Baumel, 1979).Scale bars: 0.5 cm in B; 250 mm in C-F (top); 50 mm in C-F (bottom).
(Рис.5) Overlapping contributions of NCC from the last three rhombomeres to proximal cardiac arteries. (A) The E12 chicken heart, with NCC from r6 (blue), r7 (purple) and r8 (pink) in its major arteries. (B) Graft of r6 neural folds, at HH35 (E9). Abundant quail cells (QCPN IHC, brown) are present in the aorta, magnified in C. (D) After graft of r7 neural folds, at HH35 (E9). Quail cells are visible in the outer vessel walls at the divergence of the right brachiocephalic and common carotid arteries, magnified in E. (F) After graft of r8 neural folds, at HH33 (E8.5). Left common carotid artery magnified in G. Aorta and pulmonary trunk walls magnified in H, and pericytes in the wall of the sinus venosus are indicated by arrows in I. (J) Caudal section of same embryo, showing quail NCC abundant in the aorta, in the pulmonary trunk and arteries, in the right brachiocephalic artery (magnified in K) and aortic semilunar valve (magnified in L). A, aorta; AV, atrioventricular valve; HV, hepatic vein; IVC, inferior vena cava; IVS, interventricular septum; LACV, RACV, left and right anterior cardinal veins; LBCA, RBCA, left and right brachiocephalic arteries; LCCA, RCCA,left and right common carotid arteries; LPV, left pulmonary vein (right hidden); PA, common pulmonary artery trunk; PCV, posterior cardinal vein; SA, sinoatrial valve; SL, semilunar valve; SV, sinus venosus. Scale bars: in B, 250 mm for B,D,F,I; in C, 50 mm for E,G-I,K,L.
(Рис.6) NCCs integrate into periocular and secretory tissues. (A) Parasagittal section of E12 embryo grafted with posterior diencephalic neural folds, in area of ventral eye. (B) Area enlarged shows the palatine artery with NCC-derived smooth muscle cells and a portion of the palatine membrane bone. (C) Part of a lachrymal gland, showing interstitial (arrowheads) and pericytic (arrows)participation of NCCs. (D) Lateral parasagittal section of E12 embryo grafted with anterior mesencephalic neural folds, indicating regions magnified in E-H. (E) NCC-derived pericytes (arrows) accompany the capillaries of the dorsal rectus oculomotor muscle. (F) Both glia (arrowheads) and capillary pericytes (arrows) within the optic chiasm are derived from NCCs. (G) Pericytes (arrows) are the only cells of graft origin within the neurohypophysis. (H) Both interstitial cells (arrowheads) and pericytes (arrows) in the adenohypophysis come from NCCs. Scale bars: 250 mm in A; 100 mm in B,C,E-H; 1 mm in D.
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(Рис.1) The dorsal cephalic vascular tree, excluding the jaws, ventral view. Six pairs of aortic arch arteries form during amniote embryogenesis, looping from the ventral to the dorsal aorta. Three of them persist in the adult: the third pair, as a segment of the common carotid arteries; one of the fourth pair, as the aorta; and the sixth, as a segment of the pulmonary arteries. The common carotid arteries give rise to a ventral arterial pathway, of which the internal carotid (C. i.) and derived arteries (pink) target the upper face, eyes, and forebrain. The distal part of this route is made of vascular elements derived from the first three aortic arches. The other arterial pathway in the head (green) targets the midbrain and hindbrain, and arises from the vertebral arteries (V.). Both trees start from the brachiocephalic artery trunks, which diverge from the ventral (ascending) aorta. The common carotid arteries immediately course into the neck and face. The vertebral arteries project into the head along the underside of the hindbrain after fusing to form the basilar artery. The two systems contact at the circle of Willis (box), which surrounds the optic chiasm ventral to the diencephalon. The posterior sides of this famous vascular polygon are made by the bifurcation of the basilar artery,while derivative branches of the internal carotid arteries constitute the anterior sides. An anastomotic artery, the posterior communicante (P. c.), connects them; in humans, a median fusion between the anterior cerebral arteries completes the ‘circle’. The circle of Willis represents the anatomical interface between the ventral and dorsal vascular trees. B., basilaris; C. c. a., carotis cerebralis anterior; C. c. m., carotis cerebralis medialis; C. c. p., carotis cerebralis posterior; Ce. d., cerebellaris dorsalis; Ce. v., cerebellaris ventralis;C. i., carotis interna; Eth., ethmoidalis; T. m. d., tecti mesencephalis dorsalis; T. m. v., tecti mesencephalis ventralis; V, vertebralis. Adapted, with permission, from Baumel (Baumel, 1979).
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(Рис.2) Cephalic NCCs and mesodermal cells intermingle by way of opposing dispersion patterns. (A) Section through a HH7 (4ss, early E2) embryo at level of the presumptive diencephalon. No mesodermal cells, in particular endothelial precursors (blue, Vegfr2 expression), intervene between the ectoderm and the prosencephalic alar plate. (B) Distribution of rostral-spreading NCC (red, Sox10 expression) and endothelial cells (blue, Vegfr2 expression) at early HH10 (10ss, E2) in a transverse section at the level of the anterior prosencephalon. (C) Parasagittal section of HH14 (E2) embryo, anterior right. Endothelial cells (blue, Vegfr2 expression) and NCCs (red, Sox10 expression) occupy the mesenchyme intervening between the neuroepithelium and ectoderm except around the rostral telencephalon. Sox10 is also expressed in the ventral diencephalon (see Cheng et al., 2000). Boxed region is magnified in D. (D) NCCs precede endothelial tubes as they insinuate together between the ectoderm and neuroepithelium of the telencephalon. (E) Distribution of NCCs (brown, QCPN IHC) at HH14 after a unilateral graft of an anterior mesencephalic neural fold, in transverse section at the level of the ventral diencephalon. NCCs disperse bilaterally rostral to the graft but remain unilateral near the pharynx. (F) On a slightly more anterior section of the same embryo, grafted NCCs can be seen to separate neuroepithelium from ectoderm and to be accompanied by capillaries (asterisk) as in D. (G) NCCs (arrows) from a grafted mesencephalic neural fold begin to penetrate the telencephalic neuroepithelium from the surrounding mesenchyme at HH24 (E4). Scale bars: 100 mm in A-C,E,G: 50 mm in D,F.
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(Рис.3) NCCs associated with blood vessels in the head are pericytes or smooth muscle cells. (A) Slightly oblique transverse section of an embryo grafted with an anterior mesencephalic neural fold at HH32 (E8). Quail cells are visualised with QCPN IHC in blue; a smooth muscle actin IHC is in brown. Note that blue NCCs are concentrated around the forebrain, in contrast to the rest of the central nervous system. Regions magnified in B and C are indicated. (B) Telencephalic meninges are full of quail cells, some of which penetrate the neuroepithelium and co-localise with a smooth muscle actin. (C) The double labelling of grafted cells with a smooth muscle actin within the internal carotid artery tunica media indicates that these NCCs have become smooth muscle cells (arrows). (D) Similar double-labelling within the neuroepithelial capillaries shows NCC-derived pericytes (arrows); unlabelled endothelial cells are indicated with arrowheads. Scale bars: 1 mm in A; 50 mm in B,C; 100 mm in D.
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(Рис.4) Sequential distribution of NCC from successive neural fold origins in the walls of cephalic arteries. (A) Cephalic NCCs (colours, this study) and mesoderm (greys; Le Liиvre, 1976; Couly et al., 1987) contribute to the musculo-connective wall of separate arterial trees in the head. Red corresponds to cells derived from posterior diencephalic (PD), anterior and posterior mesencephalic (AM, PM) neural folds; orange corresponds to rhombomere (r)1; yellow to r2; green to r4; turquoise to r5; and blue to r6 (in the vascular media of a schematic E7.5 chicken head). Boundaries overlap between domains ensured by NCCs of given origins in vessel walls. Within the meninges of the central nervous system, pink denotes those derived from PD, AM and PM NCCs; grey denotes those of mesodermal origin, with a sharp boundary between the two at the diencephalon/mesencephalon junction. Levels of sections shown in C-F are indicated, where lower panel is a magnification of the artery indicated in the upper panel. Levels of Fig. 3B and 3C are also shown. (B) Ink-injected E8 quail, showing both branchial and vertebral artery ramifications. (C-F) The lower panels show the enlargement of the areas boxed in the upper panels. (C) E8 chimera after graft of PD neural fold, in transverse section – internal carotid artery. (D) E8 chimera after graft of r2 neural fold, in transverse section – maxillary artery. (E) E8 chimera after graft of r4 neural fold, in transverse section – stapedian artery. Quail cells revealed by Feulgen-Rossenbeck stain (lower panel inset) are false-coloured in brown in the lower panel. (F) E8 chimera after graft of r5 neural fold, in transverse section – common carotid artery. B., basilaris; C. c. a., carotis cerebralis anterior; C. c. m., carotis cerebralis medialis; C. c. p., carotis cerebralis posterior; Ce. v.,cerebellaris ventralis; C. i., carotis interna; Eth., ethmoidalis; L., lingualis; Md., mandibularis; Mx., maxillaris; Occ., occipitalis; Oph.,ophthalmica interna; P. c., posterior communicante (circle of Willis); St., stapedia; St. te., stapedia temporalis; St. sup., stapedia supraorbitalis; T. m. v., tecti mesencephalis ventralis; V, vertebralis. Adapted, with permission, from Hughes (Hughes, 1934) and Baumel (Baumel, 1979).Scale bars: 0.5 cm in B; 250 mm in C-F (top); 50 mm in C-F (bottom).
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(Рис.5) Overlapping contributions of NCC from the last three rhombomeres to proximal cardiac arteries. (A) The E12 chicken heart, with NCC from r6 (blue), r7 (purple) and r8 (pink) in its major arteries. (B) Graft of r6 neural folds, at HH35 (E9). Abundant quail cells (QCPN IHC, brown) are present in the aorta, magnified in C. (D) After graft of r7 neural folds, at HH35 (E9). Quail cells are visible in the outer vessel walls at the divergence of the right brachiocephalic and common carotid arteries, magnified in E. (F) After graft of r8 neural folds, at HH33 (E8.5). Left common carotid artery magnified in G. Aorta and pulmonary trunk walls magnified in H, and pericytes in the wall of the sinus venosus are indicated by arrows in I. (J) Caudal section of same embryo, showing quail NCC abundant in the aorta, in the pulmonary trunk and arteries, in the right brachiocephalic artery (magnified in K) and aortic semilunar valve (magnified in L). A, aorta; AV, atrioventricular valve; HV, hepatic vein; IVC, inferior vena cava; IVS, interventricular septum; LACV, RACV, left and right anterior cardinal veins; LBCA, RBCA, left and right brachiocephalic arteries; LCCA, RCCA,left and right common carotid arteries; LPV, left pulmonary vein (right hidden); PA, common pulmonary artery trunk; PCV, posterior cardinal vein; SA, sinoatrial valve; SL, semilunar valve; SV, sinus venosus. Scale bars: in B, 250 mm for B,D,F,I; in C, 50 mm for E,G-I,K,L.
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(Рис.6) NCCs integrate into periocular and secretory tissues. (A) Parasagittal section of E12 embryo grafted with posterior diencephalic neural folds, in area of ventral eye. (B) Area enlarged shows the palatine artery with NCC-derived smooth muscle cells and a portion of the palatine membrane bone. (C) Part of a lachrymal gland, showing interstitial (arrowheads) and pericytic (arrows)participation of NCCs. (D) Lateral parasagittal section of E12 embryo grafted with anterior mesencephalic neural folds, indicating regions magnified in E-H. (E) NCC-derived pericytes (arrows) accompany the capillaries of the dorsal rectus oculomotor muscle. (F) Both glia (arrowheads) and capillary pericytes (arrows) within the optic chiasm are derived from NCCs. (G) Pericytes (arrows) are the only cells of graft origin within the neurohypophysis. (H) Both interstitial cells (arrowheads) and pericytes (arrows) in the adenohypophysis come from NCCs. Scale bars: 250 mm in A; 100 mm in B,C,E-H; 1 mm in D.