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R O'Rahilly

Publications and source records attributed to R O'Rahilly.

At least 55 records · Page 3Linked to original sources

The development of the human brain from a closed neural tube at stage 13.

Twenty-five embryos of stage 13 (28 days) were studied in detail and graphic reconstructions of seven of them were prepared. Thirty or more somitic pairs are present, and the maximum is possibly 39. The notochord is almost entirely separated from the neural tube and the alimentary epithelium, and its rostral tip is closely related to the adenohypophysial pocket. Caudal to the cloacal membrane, the caudal eminence is the site of secondary neurulation. The eminence, which usually contains isolated somites, is the area where new notochord, hindgut, and neural tube are forming. The neural cord develops into neural tube without the intermediate phase of a neural plate (secondary neurulation). Canalization is regular and the lumen is continuous with the central canal. The neural tube is now a closed system, filled with what may be termed "ependymal fluid." The brain is widening in a dorsoventral direction. Neuromeres are still detectable. The following features are distinguishable: infundibular area of D2, chiasmatic plate of D1, "adult" lamina terminalis, and commissural plate (at levels of nasal plates). The beginning of the synencephalon of D2 can be discerned. The retinal and lens discs are being defined. The mesencephalic flexure continues to diminish. The midbrain possesses a sulcus limitans, and the tegmentum may show the medial longitudinal fasciculus. The isthmic segment is clearly separated from rhombomere 1. Lateral and ventral longitudinal fasciculi are usually present in the hindbrain, and the common afferent tract is beginning. Somatic and visceral efferent fibres are seen in certain nerves: 6, 12; 5, 7, 9-11. The first indication of the cerebellum may be visible in the alar lamina of rhombomere 1. The terminal-vomeronasal crest appears. Various cranial ganglia (e.g., vestibular, superior ganglia of 9, 10) are forming. The trigeminal ganglion may show its three major divisions. Epipharyngeal placodes of pharyngeal arches 2 to 5 contribute to cranial ganglia 7, 9, and 10. The spinal neural crest is becoming segregated, and the spinal ganglia are in series with the somites. Ventral spinal roots are beginning to develop.

Brain↗

On counting cranial nerves.

The enumeration of the cranial nerves is traced briefly from Galen's seven to Willis' ten and to von Sömmerring's twelve. The system of von Sömmerring, which has been followed for some 200 years, is a useful convention, although it is merely one of several possibilities. The naming of the cranial nerves was standardized nearly 100 years ago.

Cranial Nerves↗

[The Vesalius of human embryology].

Human embryology was founded 100 years ago by WILHELM HIS, who may rightly be called the "Vesalius of human embryology". 3 landmarks were published in Germany within a quarter of a century: The Anatomie menschlicher Embryonen of HIS, KEIBEL'S Normentafeln, and KEIBEL and MALL'S Handbuch der Entwicklungsgeschichte des Menschen. The staging of the human embryo, now associated with the names of STREETER and O'RAHILLY, was first proposed by MALL in Anatomischer Anzeiger.

Embryology↗

Computer ranking of the sequence of appearance of 73 features of the brain and related structures in staged human embryos during the sixth week of development.

The sequence of events in the development of the brain in human embryos, already published for stages 8-15, is here continued for stages 16 and 17. With the aid of a computerized bubble-sort algorithm, 71 individual embryos were ranked in ascending order of the features present. Whereas these numbered 100 in the previous study, the increasing structural complexity gave 27 new features in the two stages now under investigation. The chief characteristics of stage 16 (approximately 37 postovulatory days) are protruding basal nuclei, the caudal olfactory elevation (olfactory tubercle), the tectobulbar tracts, and ascending fibers to the cerebellum. The main features of stage 17 (approximately 41 postovulatory days) are the cortical nucleus of the amygdaloid body, an intermediate layer in the tectum mesencephali, the posterior commissure, and the habenulo-interpeduncular tract. In addition, a typical feature at stage 17 is the crescentic shape of the lens cavity.

Brain↗

The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12.

Twenty-four embryos of stage 12 (26 days) were studied in detail and graphic reconstructions of five of them were prepared. The characteristic features of this stage are 21-29 pairs of somites, incipient or complete closure of the caudal neuropore, and the appearance of upper limb buds. The caudal neuropore closes during stage 12, generally when 25 somitic pairs are present. The site of final closure is at the level of future somite 31, which corresponds to the second sacral vertebral level. Non-closure of the neuropore may be important in the genesis of spina bifida aperta at low levels. The primitive streak probably persists until the caudal neuropore closes, when it is replaced by the caudal eminence or end-bud (Endwulst oder Rumpfknospe). The caudal eminence, which appears at stage 9, gives rise inter alia to hindgut, notochord, caudal somites, and the neural cord. The material for somites 30-34 (which appear in stage 13) is laid down during stage 12, and its absence would be expected to result in sacral agenesis. Aplasia of the caudal eminence results in cloacal deficiency and various degrees of symmelia. The junction of primary and secondary development (primäre und sekundäre Körperentwicklung) is probably at the site of final closure of the caudal neuropore. Secondary neurulation begins during stage 12. The cavity of the already formed spinal cord extends into the neural cord, and isolated spaces are not found within the neural cord. Primary and secondary neurulation are probably coextensive with primary and secondary development of the body, respectively. The telencephalon medium has enlarged, two mesencephalic segments (M1 and M2) are distinguishable, and rhombomere 4 is reduced. The sulcus limitans is detectable in the spinal cord and hindbrain (RhD), and in the mesencephalon and diencephalon, where it extends as far rostrally as the optic sulcus in D1. A marginal layer is appearing in the rhombencephalon and mesencephalon. The first nerve fibres are differentiating, chiefly within the hindbrain (from the nucleus of the lateral longitudinal tract). Optic neural crest is at its maximum, and the otic vesicle is giving crest cells to ganglion 7/8. Neural crest continues to develop in the brain and contributes to cranial ganglia 5, 7/8, and 10/11. The spinal crest extends as far caudally as somites 18-19 but shows no subdivision into ganglia yet. Placodal contribution to the trigeminal ganglion is not certain at stage 12. Such a contribution to ganglion 7/8 is not unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

Somitic-vertebral correlation and vertebral levels in the human embryo.

Somitic and vertebral interrelationships and levels were studied in 84 human embryos of stages 9-23 (3-8 postovulatory weeks). The first four somites are occipital, the occipitocervical junction is at somites 4/5, and eight somites are involved in the cervical region: X, Y, Z, and C. 3-7. By stage 17 the total number of occipitovertebral "units," namely 38 or 39, is attained. Resegmentation (Neugliederung) of sclerotomes is not supported. A new scheme of somitic/vertebral correlation is proposed in which somites and centra are in register. Differential growth of the regions of the vertebral column was calculated, and it was found that the percentages of the total column occupied by the various regions vary from one stage to another. The cervical and coccygeal regions decrease, the thoracic and lumbar regions increase, and the sacral region remains more or less constant during embryonic development. The following structures descend with reference to the vertebral column during the embryonic period proper: roots of lower limbs, thyroid gland and thymus, tracheal bifurcation, lungs, heart, diaphragm, abdominal arteries, mesonephroi, and suprarenal glands. The gonads may descend slightly. The scapulae and the separation point between the trachea and the esophagus remain at a fairly constant level. The metanephroi ascend. The migration of many of these structures (e.g., the heart, diaphragm, and metanephroi) is much more marked in the embryonic period than later although it continues during the fetal and postnatal periods. The conus medullaris ascends during the fetal period. Anomalies of migration that affect such organs as the thyroid gland, gonads, and metanephroi are discussed.

Embryo, Mammalian↗

The embryonic period.

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Congenital Abnormalities↗

The development of the human brain and the closure of the rostral neuropore at stage 11.

Twenty embryos of stage 11 (24 days) were studied in detail and graphic reconstructions of twelve of them were prepared. The characteristic feature of this stage is 13-20 pairs of somites. The notochord sensu stricto appears first during this stage, and its rostral and caudal parts differ in origin. Rostrally, the notochordal plate is being transformed into the notochord in a caudorostral direction. The caudal part, however, arises from the axial condensation in the caudal eminence in a rostrocaudal direction. The caudal eminence (or end bud) represents the former primitive streak. The somites are increasing in number at a mean rate of 6.6 h per pair. The rostral neuropore closes towards the end of stage 11. The closure is basically bidirectional, being more rapid in the roof region and producing the embryonic lamina terminalis and future commissural plate in the basal region. The caudal neuropore is constantly open. The brain comprises telencephalon medium (represented by the embryonic lamina terminalis) and a series of neuromeres: 2 for the forebrain (D1 and D2), 1 for the midbrain, and 6-7 for the hindbrain (RhA-C; RhD is not clearly delineated). The forebrain still occupies a small proportion of the total brain, whereas the spinal part of the neural tube is lengthening rapidly. Some occlusion of the lumen of the neural tube was noted in 4 embryos, all of which had an open rostral neuropore. Hence there is at present no evidence that occlusion plays a role in expansion of the human brain. The marginal (primordial plexiform) layer is appearing, particularly in rhombomere D and in the spinal portion of the neural tube. The neural crest is still forming from both the (open) neural groove and the (closed) neural tube, and exclusively from both neural (including optic) and (mainly) otic ectoderm. The optic sulcus is now prominent, and its wall becomes transformed into the optic vesicle towards the end of stage 11. At this time also, an optic sheath derived from mesencephalic crest and optic crest is present. The mitotic figures of the optic neural crest are exceptional in being situated in the external part of the neural epithelium. The otic pit is becoming deeper, and its wall is giving rise to neural crest that is partly added to the faciovestibulocochlear ganglion and partly forms an otic sheath. The nasal plate does not yet give off neural crest.

Brain↗

[Atlas of the stages of development of the external forms of the brain in the human embryo].

The various external features of the developing human brain during the embryonic period proper (up to 8 postovulatory weeks) are illustrated as they appear in reconstructions made from embryos of Carnegie stages 8 to 23. This is the first systematic, stage-by-stage account. The appearances are compared with those that can be seen in intact embryos of corresponding stages up to 7 postovulatory weeks. The brain of an early fetus (9 postovulatory weeks) is also included. The medial views will be treated in a subsequent article.

Atlases as Topic↗

The early origin of vertebral anomalies, as illustrated by a 'butterfly vertebra'.

An anomalous (butterfly) eleventh thoracic vertebra in a fetus of 63 mm greatest length is described and graphic reconstructions (together with normal controls) are provided. The cartilaginous hemicentra are separated by disc-like material. Cartilaginous bars to adjacent vertebrae are present. The neural arch is complete. The notochord is not duplicated. Only one comparable case in the embryonic period has been described previously. After a discussion of cleft vertebrae in the human and in experimental animals, a developmental timetable of the appearance of several vertebral anomalies is provided. The sensitive period for butterfly vertebrae, depending on the mode of origin, seems to be 3-6 postovulatory weeks. More severe anomalies, such as the split notochord syndrome, appear earlier. It is concluded that most of the vertebral anomalies discussed arise during the embryonic period proper, although the timing of a few, such as spina bifida occulta, extends into the early fetal period.

Arteries↗

The meninges in human development.

The brain and cranial meninges were studied in 61 serially sectioned embryos of stages 8-23. Much earlier stages than those examined by previous authors provided a more comprehensive view of meningeal development. As a result, the possible and probable sources of the cranial and spinal meninges are believed to be: (a) prechordal plate, (b) unsegmented paraxial (parachordal) mesoderm, (c) segmented paraxial (somitic) mesoderm, (d) mesectoderm (neural crest), (e) neurilemmal cells (neural crest), and (f) neural tube. Some of these sources (a, b, d) pertain to the cranial meninges, others (c, d, e) to the spinal coverings. The first of the future dural processes to develop is the tentorium cerebelli, which, at the end of the embryonic period proper, differs considerably in shape and composition from the later fetal and postnatal tentorium. The embryonic dural limiting layer (Duragrenzschicht) probably corresponds to the interface layer of the adult meninges. The appropriate literature was reviewed and summarized.

Arachnoid↗

The first appearance of the neural tube and optic primordium in the human embryo at stage 10.

Thirteen embryos of stage 10 (22 days) were studied in detail and graphic reconstructions of most of them were prepared. The characteristic feature of this stage is 4-12 pairs of somites. Constantly present are the prechordal and notochordal plates (the notochord sensu stricto is not yet apparent), the neurenteric canal or at least its site, the thyroid primordium, probably the mesencephalic and rhombencephalic neural crest and the adenohypophysial primordium. During this stage, the following features appear: terminal notch, optic sulcus, initial formation of neural tube, oropharyngeal membrane, pulmonary primordium, cardiac loop, aortic arches 1-3, intersegmental arteries, and laryngotracheal groove. The primitive streak is still an important feature. Graphic reconstructions have permitted the detection of the telencephalic portion of the forebrain, for the first time at such an early stage. It is proposed that the remainder of the forebrain comprises two subdivisions: D1, which becomes largely the optic primordium during stage 10, and D2, which is the future thalamic region. The optic sulcus is found in D1 but does not extent into D2, as has been claimed in the literature. An indication of invagination of the otic disc appears towards the end of the stage. As compared with the previous stage, the prosencephalon has increased in length, the mesencephalon has remained the same, the rhombencephalon has decreased, and the spinal part of the neural plate has increased fivefold in length. The site of the initial closure of the neural groove is rhombencephalic, upper cervical, or both. The neural plate extends caudally beyond the site of the neurenteric canal. Cytoplasmic inclusions believed to indicate locations of great activity were always detected in the forebrain (especially in the optic primordium), and also in the rhombencephalon, spinal part, and mesencephalon.

Brain↗

The development and classification of anomalies of the limbs in the human.

It is stressed that more detailed and more precise information concerning the human limb is available than is found in even the most recent books on the development of the vertebrate limb. The classifications of limb anomalies are multiplying but are not necessarily becoming better. In addition to continued vigilance concerning possible teratogens, the most valuable approach in the human is the superimposition of genetic data (where they exist) onto a detailed classification based on sound morphology and current principles of anatomical terminology.

Animals↗

The origin of the ectodermal ring in staged human embryos of the first 5 weeks.

Seven embryos of stages 10-16 (3-5 weeks) were studied for their external form by means of graphic reconstructions. This is the first systematic report on the general surface anatomy of the early human embryo. The brain has been described and illustrated in a previous publication, and the present article is concerned particularly with an important although neglected feature: the ectodermal ring, described by Schmitt [Morph. Arb., Jena 8: 236-303, 1898] and named by Blechschmidt [Funktionsentwicklung. I. Mechanische Gegenwirkungen. Musterschmidt, Göttingen 1948]. Late in stage 10, three longitudinal bands can be seen on the surface: somitic, intermediate, and lateral plate. The intermediate band, which partly overlies nephrogenic tissue, is the site of the future ectodermal ring, which begins as an inverted U at stage 11 and is completed caudally in stage 12. The ectodermal ring, which may well be an important example of epithelial-mesenchymal interaction, comprises six parts: (a) rostral part, containing the situs neuroporicus, and olfactory and lens discs; (b) pharyngeal part, the covering of the pharyngeal arches; (c) occipital and cervicothoracic parts, related at first to the four occipital somites and later to the cervicothoracic junction; (d) membral part, represented by a preliminary ectodermal thickening, followed within 2 days by the apical ectodermal ridge; (e) intermembral part, related at first to the underlying coelom, and mesonephric duct and ridge; (f) caudal part, containing the cloacal membrane and a temporary 'caudal ectodermal ridge'. It is stressed that the incorrectly named 'Milchstreifen' is merely the intermembral part, in which the mammary crest ('Milchlinie' or 'Milchleiste') appears 1 week later.

Ectoderm↗

The early development of the hypoglossal nerve and occipital somites in staged human embryos.

Serial sections of 105 human embryos (including 20 silver preparations) from stage 11 (24 days) to stage 22 (54 days) were studied, and 23 graphic reconstructions were prepared. The hypoglossal nucleus is evident at stage 12 and becomes isolated from other efferent nuclei at stage 14. The first hypoglossal nerve fibers appear at stage 12. The roots unite at stage 14 and the main trunk arrives in the tongue at stage 15. Four occipital somites can be identified during stage 13, and the sclerotomic material forms two bilateral masses. The fourth sclerotome separates in stage 14 and develops like a vertebra. This and the remaining sclerotomic material form the basioccipital and exoccipital parts of the chondrocranium , which are the first to appear. Four occipital myotomes develop and grow towards the tongue as the "hypoglossal cord", which arrives prior to the hypoglossal nerve. The developmental similarity in the hypoglossal region between birds and mammals, combined with experimental studies in birds, renders it extremely likely that the hypoglossal musculature in mammals also is derived from occipital somites. The present study is the first in which this conclusion is adequately supported in the human. This investigation aids in the interpretation and timing of origin of variations (e.g., bipartite hypoglossal canal) and anomalies (e.g., persistent hypoglossal artery).

Gestational Age↗

Computer ranking of the sequence of appearance of 100 features of the brain and related structures in staged human embryos during the first 5 weeks of development.

The sequence of events in the development of the brain in staged human embryos was investigated in much greater detail than in previous studies by listing 100 features in 165 embryos of the first 5 weeks. Using a computerized bubble-sort algorithm, individual embryos were ranked in ascending order of the features present. This procedure made feasible an appreciation of the slight variation found in the developmental features. The vast majority of features appeared during either one or two stages (about 2 or 3 days). In general, the soundness of the Carnegie system of embryonic staging was amply confirmed. The rhombencephalon was found to show increasing complexity around stage 13, and the postoptic portion of the diencephalon underwent considerable differentiation by stage 15. The need for similar investigations of other systems of the body is emphasized, and the importance of such studies in assessing the timing of congenital malformations and in clarifying syndromic clusters is suggested.

Brain↗