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Biomedical subjects

M L Kirby

Publications and source records attributed to M L Kirby.

At least 19 recordsLinked to original sources
PubMed1992

Migration and distribution of circumpharyngeal crest cells in the chick embryo. Formation of the circumpharyngeal ridge and E/C8+ crest cells in the vertebrate head region.

The cardiac neural crest is located in a transitional area on the neuraxis between trunk and cephalic regions and gives rise to both the dorsolateral and ventrolateral crest cell populations. Around stage 18 of chick development, a mass of E/C8+ cells surrounds the postotic pharyngeal arches and forms a crescent-shaped arch, termed the circumpharyngeal ridge. Using immunohistochemistry and quail-chick chimeras, it was determined that the E/C8+ cell mass located in the circumpharyngeal ridge derives from the dorsolateral component of the cardiac neural crest. The ventrolateral cell population of the cardiac crest is located more medially and shows long-persistent HNK-1 immunoreactivity dorsolateral to the foregut. The crest cells that populate the gut arise from the caudal portion of the circumpharyngeal crest and are always located caudal to the caudal-most pharyngeal ectomesenchyme. Circumpharyngeal crest cells continuously populate the pharyngeal arch ectomesenchyme and enteric nervous system on the lateral side of the foregut wall, as well as the hypoglossal pathway which develops within the ventral portion of the circumpharyngeal ridge. E/C8 and HNK-1 immunoreactivity are associated with the cells migrating via the dorsolateral (circumpharyngeal) and ventrolateral pathways, respectively, with one exception: there is a population of putative crest cells along the proximal course of the vagal intestinal branch that shows both immunoreactivities around stage 20. DiI labeling of the cells in the circumpharyngeal ridge suggests that the cells are contributed from the circumpharyngeal ridge to this population. Thus, the distribution of the circumpharyngeal crest cells and their derivatives coincides with the peripheral branch distribution of the cranial nerves IX, X, and XII, whose development is selectively affected in the absence of the cardiac neural crest, the source of the circumpharyngeal crest.

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PubMed1991

Initial migration and distribution of the cardiac neural crest in the avian embryo: an introduction to the concept of the circumpharyngeal crest.

The distribution and migration of the cardiac neural crest was studied in chick embryos from stages 11 to 17 that were immunochemically stained in whole-mount and sectioned specimens with a monoclonal antibody, HNK-1. The following results were obtained: 1) The first phase of the migration in the cardiac crest follows the dorsolateral pathway beneath the ectoderm. 2) In the first site of arrest, the cardiac crest forms a longitudinal mass of neural-crest cells, called in the present study, the circumpharyngeal crest; this mass is located dorsolateral to the dorsal edge of the pericardium (pericardial dorsal horn) where splanchnic and somatic lateral mesoderm meet. 3) A distinctive strand of neural-crest cells, called the anterior tract, arises from the mid-otic level and ends in the circumpharyngeal crest. 4) By stage 16, after the degeneration of the first somite, another strand of neural-crest cells, called the posterior tract, appears dorsal to the circumpharyngeal crest. It forms an arch-like pathway along the anterior border of the second somite. 5) The seeding of the pharyngeal ectomesenchyme takes place before the formation of pharyngeal arches in the postotic area, i.e., the crest cells are seeded into the lateral body wall ventrally from the circumpharyngeal crest; and, by the ventral-ward regression of the pericardial dorsal horn, lateral expansion of pharyngeal pouch, and caudal regression of the pericardium, the crest cell population is pushed away by the pharyngeal pouch. Thus the pharyngeal arch ectomesenchyme is segregated. 6) By stage 14, at the occipital somite level, ventrolateral migration of the neural crest is observed within the anterior half of each somite. Some of these crest cells are continuous with the caudal portion of the circumpharyngeal crest. An early contribution to the enteric neuroblasts is apparent in this area.

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PubMed1991

Temporospatial study of the migration and distribution of cardiac neural crest in quail-chick chimeras.

It has been demonstrated that the septation of the outflow tract of the heart is formed by the cardiac neural crest. Ablation of this region of the neural crest prior to its migration from the neural fold results in anomalies of the outflow and inflow tracts of the heart and the aortic arch arteries. The objective of this study was to examine the migration and distribution of these neural crest cells from the pharyngeal arches into the outflow region of the heart during avian embryonic development. Chimeras were constructed in which each region of the premigratory cardiac neural crest from quail embryos was implanted into the corresponding area in chick embryos. The transplantations were done unilaterally on each side and bilaterally. The quail-chick chimeras were sacrificed between Hamburger-Hamilton stages 18 and 25, and the pharyngeal region and outflow tract were examined in serial paraffin sections to determine the distribution pattern of quail cells at each stage. The neural crest cells derived from the presumptive arch 3 and 4 regions of the neuraxis occupied mainly pharyngeal arches 3 and 4 respectively, although minor populations could be seen in pharyngeal arches 2 and 6. The neural crest cells migrating from the presumptive arch 6 region were seen mainly in pharyngeal arch 6, but they also populated pharyngeal arches 3 and 4. Clusters of quail neural crest cells were found in the distal outflow tract at stage 23.

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PubMed1991

Development of cranial nerves in the chick embryo with special reference to the alterations of cardiac branches after ablation of the cardiac neural crest.

Development of cranial nerve branches in the cardiac region was observed in whole-mount specimens which were stained with a monoclonal antibody, E/C8, after the ablation of the cardiac neural crest. In early embryos, nerve trunks of IX and X were lacking or only poorly developed, while the early development of pharyngeal branch primordia was normal. In day 5 embryos, the nerve trunks of IX-X were present in all the embryos, however; extensive communication was observed between X and XII. On day 6 and later, the spiral pattern of superior cardiac branches was disturbed, as were the blood vessels. Furthermore, the distal branches of XII passed within the superficial layer of cardiac outflow mesenchyme. Vagal branches passed within the deeper layer. There was no apparent change in the development of the sinal branch. Using quail--chick chimeras, it was found that the cardiac neural crest cells formed the Schwann cells of XII, and that they were also associated with the hypobranchial muscle primordium, suggesting that the absence of the cardiac neural crest not only disturbs the development of the cardiac outflow septation, but also affects the normal morphogenesis of the hypobranchial musculature and its innervation. Embryologically, the tongue is located close to the cardiac outflow tract, which is the migration pathway of the cardiac neural crest-derived cells.

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PubMed1991

Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos.

BACKGROUND: Microcinephotography was used to study a model of persistent truncus arteriosus created in chick embryos by ablation of premigratory neural crest destined for the third and fourth aortic arch arteries as well as the septum of the cardiac outflow tract. METHODS AND RESULTS: Twenty-five control embryos and 105 of 202 experimental embryos were filmed on day 3 of incubation and then reincubated. The remaining 97 experimental embryos were not filmed because of twisting of the embryos, but they were reincubated. There was no difference in either the survival rate (p greater than 0.23) from day 3 to day 11 of incubation or the incidence of persistent truncus arteriosus (p greater than 0.08) between the filmed and the nonfilmed embryos. Incomplete looping of the cardiac tube observed in experimental embryos during early cardiogenesis correlated with a right ventricular origin of the outflow vessels in the definitive heart. Hemodynamic measurements indicated that there was no difference in heart rate, ejection fraction, systolic and diastolic areas, stroke volume, and cardiac output between controls and the experimental group as a whole. However, embryos that did not survive to day 11 had decreased stroke volume (p less than 0.001) and cardiac output (p less than 0.001), whereas embryos that survived to day 11 with cardiac malformations had increased stroke volume and cardiac output in early embryogenesis. CONCLUSIONS: Increased stroke volume and cardiac output may be necessary factors for survival in embryos with cardiac dysmorphogenesis and probably are associated with dilation of the ventricular portion of the cardiac tube, which leads to malalignment of the outflow vessel or vessels.

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PubMed1991

Hemodynamic changes and compensatory mechanisms during early cardiogenesis after neural crest ablation in chick embryos.

Microcinephotography was used to study early heart development in chick embryos with ablations of the neural crest known to result in persistent truncus arteriosus with associated aortic arch anomalies. The premigratory neural crest destined for the 3rd and 4th pharyngeal arches and the aorticopulmonary septum were ablated. When the embryos reached the looped cardiac tube stage (stage 18), 15 experimental and 15 control embryos were filmed at 100 frames/s under controlled environmental conditions. End-diastolic and end-systolic dimensions were determined for the conotruncus and presumptive right ventricle that together compose the bulbus cordis. The results showed that the shortening fractions and ejection fractions were significantly depressed in the experimental embryos. The experimental embryos exhibited dilation and decreased emptying of the ventricle. There was no difference in heart rate or stroke volume between the control and experimental embryos. Thus, the calculated cardiac output was the same in the control and experimental groups. It appeared that the experimental embryos compensated for decreased contractility by ventricular dilation. These functional compensations in very early cardiac development may play an etiologic role in the subsequent development of structural heart defects.

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PubMed1990

Origin of the proximal coronary artery stems and a review of ventricular vascularization in the chick embryo.

The objective of this study was to determine how the coronary artery stems develop in the chick embryo. The hearts of 51 ink-injected and cleared chick embryos, aged embryonic days 6, 6.5, 7, 7.5, 9, and 10, were dissected, examined, and selectively photographed. Two representative hearts from each group were paraffin embedded, serially sectioned at 10 microns, and examined for aortic endothelial budding. We found that the proximal coronary artery did not appear to grow outward from the aorta as commonly described in the literature. It appeared to originate from a capillary ring which encircled the aortic and pulmonary outflow tracts. On embryonic day 7.5, one to three channels arising from this ring penetrated each aortic sinus, in an area of darker textured endothelium. Histologically and grossly, multiple channels were still apparent on day 9, particularly in the left coronary artery. One of these channels always became dominant to form the stem. Each stem, which varied in length from embryo to embryo, always ended in a plexus of sinusoidal endothelial tubes. By day 10, the coronary artery stems were longer, with many major branches. Histologically, evidence of multiple channels still was visible. It is significant that channels from the bulbar vascular ring penetrated the aorta at very specific points in the aortic sinuses and did not penetrate the pulmonary trunk or other aortic sites. We believe this fact indicates that the penetration of the aortic sinuses by channels from the bulbar vascular ring represents a controlled invasion of the aorta.

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PubMed1990

The effects of high phenylalanine concentration on chick embryonic development.

Cells from a particular portion of the cranial neural crest (cardiac neural crest) migrate from the neural fold into pharyngeal arches 3, 4 and 6, where they provide the support for the endothelium of the aortic arch arteries, and by migration into the outflow tract become involved in septation of the truncus arteriosus. Ablation of the premigratory cardiac neural crest results in persistent truncus arteriosus and other defects reminiscent of the DiGeorge syndrome in man. Removal of a small area of the cardiac neural crest causes a spectrum of heart defects classified together as dextraposed aorta including changes like that of Fallot's tetralogy in man. Some inflow tract anomalies have also been found. Pilot studies injecting phenylalanine into developing chick embryos at a very early stage had little effect on embryo viability or on the incidence of congenital heart defects. However, sham-treated animals produced predominantly small simple ventricular septal defects but phenylalanine-treated embryos had more serious and complex heart anomalies. It is not possible to say yet that congenital heart disease in the offspring of mothers with untreated phenylketonuria is due to phenylalanine-induced damage to the neural crest, but the pilot studies in chick suggest that this idea is worth pursuing.

Animals↗
PubMed1990

Actin and myosin isoforms in aneural and malformed chick hearts.

Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiovascular system, by removing various regions of the neural crest from early embryos. The neural crest provides both neural (sympathetic and parasympathetic) and ectomesenchymal components to the heart, and selective removal of various areas results in embryos with sympathetically aneural hearts, or persistent truncus arteriosus with or without parasympathetic denervation. Myosin isoform expression was studied in each of these types of hearts using an array of myosin antibodies specific for atrium, ventricle or the conduction system. Myosin expression in experimental hearts was found to follow the normal pattern of development using these antibodies. Actin expression was studied using cDNA probes for the 3' untranslated region of actin mRNA of the alpha-skeletal, alpha-cardiac and beta-actin isoforms. Using slot-blot hybridization analysis, the pattern of actin expression in atrium and ventricle was followed throughout the period of incubation in normal hearts. The pattern of actin expression was found to be abnormal in hearts which were sympathetically aneural and those which had persistent truncus arteriosus combined with parasympathetic denervation. ATPase activity was increased only in atria of hearts with persistent truncus arteriosus. It appears from these experiments that actin isoform expression is influenced in the chick heart by autonomic innervation.

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PubMed1990

Microcinephotography of the developing heart in neural crest-ablated chick embryos.

Microcinephotography was used to study heart development in a neural crest model of heart defects, that is, persistent truncus arteriosus, interrupted aortic arch, double outlet right ventricle, or single ventricle and tricuspid valve anomalies. These defects were created in chick embryos by ablation of premigratory neural crest destined for the aorticopulmonary and truncal septa, as well as the third and fourth aortic arch arteries. When embryogenesis reached the looped cardiac tube stage of development (Hamburger-Hamilton stage 18), 19 experimental and 15 control embryos were filmed at 100 frames per second under controlled environmental conditions. Analysis of the microcinephotography films showed the following significant distinguishing characteristics of the developing heart in the experimental embryos: altered conotruncal shape in 100%, depressed contractility and dilation of the primitive ventricle in 84%, decreased emptying of the bulbus cordis in 79%, incompetent truncal cushions in 68%, incomplete looping of the cardiac tube in 58%, and fourth right aortic arch artery without blood flow and third right aortic arch artery with increased flow in 53%. These abnormal characteristics suggested that there were functional and morphological changes in the developing heart of experimental embryos before the time when the predicted structural heart defects would be apparent. It is proposed that the primitive ventricle might attempt to compensate for depressed contractility by ventricular dilation. The incompetent truncal cushions could be secondary to the depressed contractility or secondary to the neural crest ablation that is known to cause persistent truncus arteriosus, an interrupted aortic arch, or both. The absence of blood flow in the right fourth aortic arch artery that will become the definitive aorta correlates with the expected incidence of interrupted aortic arches in this neural crest-ablation model of heart defects. It is speculated that the incomplete looping of the cardiac tube might hinder normal developmental alignment of the outflow and inflow tracts, producing a spectrum of lesions of maldevelopment of the tricuspid valve and dextroposition of the aorta.

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PubMed1989

Chronotropic responses of chick atria to field stimulation after various neural crest ablations.

Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, parasympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed by a variety of morphological and biochemical methods, but the functional status of innervation is not known. In the present study, we have used electrocardiography and field stimulation to determine the functional neural status of the three different innervation models. The RR and QTc intervals were measured to assess the dominant autonomic tone and autonomic dysfunction in the heart. Even though the RR and QTc intervals were found to be identical in sham and experimental embryos, field stimulation of superfused atria showed that the sympathetically aneural heart has functional cholinergic innervation but lacks any sympathetic response. Hearts from embryos which were parasympathetically aneural lacked a cholinergic response to field stimulation and were judged to be functionally parasympathetically aneural. Hearts with cholinergic ganglia reconstituted from the nodose placodes have normal RR and QTc intervals as well as a normal cholinergic response to field stimulation. The results indicate that these neurons are functionally indistinguishable from neural crest-derived neurons.

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