Immunolocalization of N‐CAM in the heart of the early developing rat embryo

Okagawa, Hiroto; Nakagawa, Masao; Simada, Morimi

doi:10.1002/ar.1092430213

Cited by 12 publications

(8 citation statements)

References 22 publications

(33 reference statements)

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“…In the vessel wall NCAM is most likely involved in vasculogenesis, by the homing of neural crest cells, as has been described before (20,21) NCAM is reported to diminish after neural crest cells have ceased migration (17). Migration of cardiac neural crest cells is needed for normal cardiovascular development.…”

Section: Discussionmentioning

confidence: 74%

Increased NCAM Expression and Vascular Development in Trisomy 16 Mouse Embryos: Relationship with Nuchal Translucency

et al. 2005

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Increased nuchal translucency in the human fetus is associated with chromosomal abnormalities, enlarged jugular lymphatic sacs, cardiac defects and changed flow through the ductus venosus. The developmental background of this nuchal edema in relation to the associated anomalies remains elusive. We studied the morphologic correlation between neurogenesis and vasculogenesis in neck, heart, and ductus venosus region of wild type and trisomy 16 mice embryos (E10-E18), using an antibody against Neural Cell Adhesion Molecule (NCAM). Trisomy 16 mice are a model for the above described human phenotype. From E12 trisomy 16 mice showed an altered arrangement of cranial nerves IX, X and XI, which are positioned between the carotid artery, jugular vein and enlarged lymphatic sac. The vagal nerve was significantly smaller, compared with wild type embryos. NCAM was over expressed in both neuronal and cardiovascular structures in trisomy 16 mice, being particularly prominent in the 4 th and 6 th pharyngeal arch arteries, and the ductus venosus. In the 4 th and 6 th pharyngeal arch arteries, NCAM over expression was located to the part of the vessel wall that is closely related to the vagal and recurrent nerve. In case of 4 th pharyngeal arch artery abnormalities NCAM expression, on the other hand, was reduced. In conclusion, the interaction between neurogenesis and vasculogenesis is disturbed in the trisomy 16 mouse model, and might be a common denominator in the spectrum of anomalies associated with increased nuchal translucency. Ultrasonographic measurement of nuchal translucency (NT) in the human fetus at gestational age between 10 to 14 wk is a common screening method to detect trisomy 21. Increased NT is associated with a spectrum of anomalies, including aneuploidy, isolated cardiac defects, and changed flow velocities through the ductus venosus (1,2).The developmental background of increased NT and associated findings is still insufficiently understood. Recently, a disturbed lymphangiogenesis has been suggested as a basis for the nuchal edema because of the concomitant abnormal enlargement and persistence of the jugular lymphatic sacs (JLS) in both human fetuses and mouse embryos with nuchal edema (3,4). This theory explains both the regional accumulation of the fluid in the neck region and the temporary character of the NT enlargement. Other suggested theories, like temporary cardiac failure (5,6) and the alteration of extracellular matrix components (7) might be part of the causal pathway, but fail to completely elucidate this phenomenon.A study (3) of trisomy 16 embryos showed that the endothelium of the enlarged JLS was abnormally thickened. Also, there was a very close correlation of nerves with the JLS and other vascular structures. A mutual influence of nerves and endothelium could play a role in the development of nuchal translucency, since vessels and nerves are known to share many developmental genes (8).The hypothesis for this study was that a disturbance in the interaction between neurogenesis and vasculogene...

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Section: Discussionmentioning

confidence: 74%

Increased NCAM Expression and Vascular Development in Trisomy 16 Mouse Embryos: Relationship with Nuchal Translucency

et al. 2005

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“…This study describes the morphology and incidence of cardiovascular defects induced by bis-diamine in Sprague-Dawley (SD) and Wistar rats. Remarkable differences in heart anomalies were observed between the two strains and an immunohistological study using an antineural cell adhesion molecule (N-CAM) antibody, which is an excellent marker for migrating neural crest cells (Okagawa et al . 1995;Fujino et al .…”

Section: Introductionmentioning

confidence: 99%

Morphological differences in cardiovascular anomalies induced by bis‐diamine between Sprague–Dawley and Wistar rats

Fujino

Nakagawa

Nishijima

et al. 2005

Congenital Anomalies

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It is known that animals show different responses to the same teratogen between different strains. We examined cardiac malformations in Sprague-Dawley (SD) and Wistar rats induced by bis-diamine, which produced conotruncal anomalies and aortic arch malformations in embryos when administered to the dams, to elucidate the morphological differences and pathogenesis in the two strains. Two hundred milligrams of bis-diamine dissolved in 1% gum-tragacanth was administered to pregnant rats on embryonic day (ED) 9.5, 10.5 and 11.5 in each strain. The embryos were removed on ED 20.5. External appearances, cardiovascular morphology and associated anomalies were examined under a dissecting microscope. An immunohistological study with an anti-N-CAM antibody, an excellent marker for neural crest cells, was performed on ED 12.5 embryos. Isolated aortic arch anomalies were common features of malformations induced by bis-diamine in SD rats and intracardiac defects were found in a small number of the embryos. Wistar rats showed more serious cardiovascular anomalies, such as persistent truncus arteriosus and tetralogy of Fallot, especially when dams were treated on ED 10.5 and isolated arch anomalies were significantly less prevalent than in SD rats. Immunohistology demonstrated that there were fewer N-CAM positive cells in the conotruncal region in Wistar rats than in SD rats. Bis-diamine induced more critical cardiovascular malformations in Wistar rats because neural crest cells, which play an important role in conotruncal septation, were more extensively damaged. Different susceptibility to bis-diamine and/or different time of neural crest cell emigration from the hindbrain might explain those morphological differences.

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“…As both HNK-1 and N-CAM are coincident markers of neural tissue-derived cells (Bronner-Fraser et al, 1992;Okagawa et al, 1995), these findings suggest that bis-diamine reduces the number of neural crest cells migrating to participate in the conotruncal septation, which may be caused by the delay in neural tube development. Recently, Jiang et aZ.…”

Section: Development: In Vzvomentioning

confidence: 84%

Teratogenic effect of bis‐diamine on embryonic rat heart

Nakagawa

Nishijima

Fujino

et al. 2000

Congenital Anomalies

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Bis‐diamine induces conotruncal anomalies including persistent truncus arteriosus, tetralogy of Fallot, interruption of the aortic arch, and ventricular septal defect in rat embryos when administered to the mother. Bis‐diamine also induces extracardiac malformations including thymic hypoplasia, facial dysmorphism, forelimb anomalies and diaphragmatic hernia. However, the teratogenic mechanisms of this chemical in early developing rat hearts have not been fully established. Chimeric studies in chick and quail embryos demonstrated that the cranial neural crest cells reached the cardiac outflow tract, contributing to aorticopulmonary and truncal septation. Since an ablation of the cranial neural crest also produced the conotruncal anomalies, bis‐diamine is proposed to disturb the normal migration of cardiac neural crest cells to the heart. Based on our data concerning cardiac anomalies induced by bis‐diamine, we reviewed how the cardiac malformations were morphologically established in early developing rat hearts. Our data showed that 1) cardiovascular anomalies induced by bis‐diamine are time‐ and species or strain‐ dependent. 2) bis‐diamine reduces the number of neural crest cells migrating to participate in the conotruncal septation, 3) bis‐diamine induces anomalous coronary arteries, thin ventricular walls and epicardial defects, and 4) some embryos cultured in the medium containing bis‐diamine had extra‐cardiac abnormalities including abnormal location of the otic placodes and delay in mid brain closure. Conclusively, bis‐diamine does not appear to merely affect the cardiac development, but rather disturbs normal development of all the organs contributed to by neural crest cells.

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Immunolocalization of N‐CAM in the heart of the early developing rat embryo

Cited by 12 publications

References 22 publications

Increased NCAM Expression and Vascular Development in Trisomy 16 Mouse Embryos: Relationship with Nuchal Translucency

Increased NCAM Expression and Vascular Development in Trisomy 16 Mouse Embryos: Relationship with Nuchal Translucency

Morphological differences in cardiovascular anomalies induced by bis‐diamine between Sprague–Dawley and Wistar rats

Teratogenic effect of bis‐diamine on embryonic rat heart

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