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Biomedical subjects

R O'Rahilly

Publications and source records attributed to R O'Rahilly.

At least 73 records · Page 4Linked to original sources

Embryonic length and cerebral landmarks in staged human embryos.

The greatest length (GL) and the crown-rump (C-R) length were compared in 43 staged human embryos. It was found that point C, which overlies the middle of the midbrain, was sometimes difficult to locate and that point R is not precise. These disadvantages render the C-R measurement unsatisfactory. At 4 weeks (stage 13) the GL comes to exceed the C-R and continues to do so until about 7 weeks (stages 17-19). The maximum difference is approximately 1.5 mm. Thereafter, the two lengths are basically equal and coincide from about stages 18 and 19 onward. In a series of 100 embryos of stages 19-23, female embryos at stages 21 and 22 were found to be shorter (by a mean of 1 mm) than male embryos, but not at stages 19, 20, and 23. The greatest length, which is independent of fixed points, is much simpler to measure than the C-R length, and it is recommended that it be used instead. It is pointed out that Streeter had already made that substitution. The greatest length has the further advantage of being a practicable measurement from two postovulatory weeks (stage 6) throughout the remainder of the embryonic and also in the fetal period. The lower limbs are excluded from measurement.

Anthropometry↗

Cerebral dysraphia (future anencephaly) in a human twin embryo at stage 13.

Cerebral dysraphia was studied histologically and by graphic reconstruction in a twin at stage 13, and comparisons were made with the normal (discordant) twin. The normal, bidirectional closure of the rostral neuropore was investigated in several embryos, from which it was concluded that the situs neuroporicus is represented by the future commissural plate rather than by the (adult) lamina terminalis. In the abnormal twin the neural tube was open over part of the midbrain and forebrain, although the situs neuroporicus was closed. The experimental production of anencephaly by Giroud and co-workers was reviewed, and comparisons between embryonic staging systems in the rat, mouse, and human were made. Three corresponding phases are found in the human: 1) cerebral dysraphia, occurring before or during Carnegie stage 11 (approximately 23-25 days); 2) exposure of a highly developing and well-differentiated brain during the remainder of the embryonic period; and 3) degeneration of the exposed brain throughout the fetal period, resulting in anencephaly. Hence the abnormal twin described here is believed to represent a precursor of typical anencephaly, and is the earliest example of purely cerebral dysraphia so far recorded.

Anencephaly↗

The first appearance of the major divisions of the human brain at stage 9.

Five embryos of stage 9 (20 days) were studied in detail and graphic reconstructions were prepared. This is the first report based on more than one specimen of this rarely seen stage. Detailed measurements of the embryos are provided. The characteristic features of this stage are 1 to 3 pairs of somites, the head fold and foregut, the otic discs, and the pericardial cavity. The primitive streak is not decreasing as rapidly as in stage 8 but the caudal eminence is proliferating. The notochordal plate is not increasing as rapidly as in stage 8 and a notochord is not yet present. It is to be stressed that the 3 major divisions of the brain (prosencephalic, mesencephalic, and rhombencephalic) can be identified in the open neural groove. The rhombencephalon is the dominant feature of the brain and comprises 4 subdivisions, the last of which, previously unrecognized, is related to the (occipital) somites and represents the hypoglossal region. Features that may not be visible include the caudal fold and hindgut, endocardial tubes or plexus, neural crest, and neurenteric canal. In 2 specimens, atria, left ventricle, right ventricle, conotruncus, and first (or first and second) aortic arches are distinguishable. Two of the embryos studied are the earliest examples in which neural crest has been identified.

Brain↗

The human vertebral column at the end of the embryonic period proper. 2. The occipitocervical region.

The present investigation of the cervical region of the vertebral column at eight post-ovulatory weeks is the first such study based on precise reconstructions of staged embryos. At the end of the embryonic period proper, a typical vertebra is a U-shaped piece of cartilage characterized by spina bifida occulta. The notochord ascends through the centra and leaves the dens to enter the basal plate of the skull. The median column of the axis comprises three parts (designated X, Y, Z) which persist well into the fetal period. They are related to the first, second and third cervical nerves, respectively. Part X may project into the foramen magnum and form an occipito-axial joint. Part Z appears to be the centrum of the axis. The articular columns of the cervical vertebrae are twofold, as in the adult: an anterior (atlanto-occipital and atlanto-axial) and a posterior (from the lower aspect of the axis downwards). Alar and transverse ligaments are present. Cavitation is not found in the embryonic period in either the atlanto-occipital or zygapophysial joints, and is generally not present in the median atlanto-axial joint either. Most of the transverse processes exhibit anterior and posterior tubercles. An 'intertubercular lamella' may or may not be present, i.e. the foramina transversaria are being formed around the vertebral artery. The spinal ganglia are generally partly in the vertebral canal and partly on the neural arches, medial to the articular processes. During the fetal period, the articular processes shift to a coronal position and this alteration appears to be associated with a corresponding change in the location of the spinal ganglia.

Atlanto-Axial Joint↗

Myelination of the human fetal phrenic nerve.

The formation of the myelin sheath of the human phrenic nerve has been studied by electron microscopy in fetuses aged 15, 17, and 23 postovulatory weeks. At 15 weeks, the phrenic nerve is composed mainly of large bundles of axons surrounded by lemmocyte processes. However, fibres at the beginning of myelination are present and show one or one and a half turns of lemmocyte process. At 17 weeks, an increasing number of myelinating fibers can be noted, and the formation of compact myelin and laminated perineurium is detectable. The phrenic nerve presents a mature form by 23 postovulatory weeks. At this time many axons have acquired a thick, compact myelin sheath. However, fibres at early stage of myelin formation are still visible.

Fetus↗

[Atlas of the stages of development of the nervous system in the intact human embryo].

Many features of the developing nervous system are visible in the intact human embryo, and a photographic atlas from 3-7 postovulatory weeks (stages 10-19) is provided. A number of features, such as the cerebellar plate, the cerebral vesicles, and the epiphysis cerebri, can be detected on external views at as early a stage as they have previously been recorded after microscopical examination. After 7 weeks it becomes increasingly difficult to identify features of the brain from the surface.

Anatomy↗

An electron microscopic study of myelination of pyramidal fibres at the level of the pyramidal decussation in the human fetus.

The ultrastructure of pyramidal fibres at the level of the pyramidal decussation was studied in a 23 week-old human fetus (220 mm. C.-R.). It was found that the fibres are mainly unmyelinated. However, well-myelinated fibres were scattered above the pyramidal decussation and they were also present below the decussation in both the anterior and the lateral corticospinal tract. Within the tracts, well-differentiated glial cells were observed.

Axons↗

The estimated age of staged human embryos and early fetuses.

The appearance of anatomic features during embryogenesis relative to menstrual history is not well established. The 621 staged human embryos and fetuses in the Carnegie Embryological Collection were examined, and morphologic features were recorded in 494 specimens in good condition, from 382 intrauterine, 49 ectopic, and 55 pregnancies of other or unknown source. There were menstrual data on 276 specimens, and for 10 the date of a single coitus was known. The embryo develops to 1 mm at the twenty-eighth menstrual day, after which its crown-rump length increases by 0.7 mm per day. Coital ages and postovulatory ages estimated from menstrual data correlated significantly (p less than 0.001) with crown-rump length and Carnegie stage, but estimated postovulatory age was highly variable (standard deviation, 10.5 days). Morphologic features appeared within a narrow interval (standard deviation, 0.0 to 1.5 Carnegie stages). Normal human embryogenesis is a stereotyped sequence with little statistical variation, but menstrual data in individual cases may be unreliable in dating this sequence.

Coitus↗

The growth of the human brain during the embryonic period proper. 1. Linear axes.

Linear axes of the brain were measured in 143 human embryos from Carnegie stages 11 to 23 (3 1/2-8 postovulatory weeks). The embryos ranged from 3 to 30 mm in C.-R. length. Both Born reconstructions and serial sections of the central nervous system were used. The brain axes included were the fronto-occipital diameter, bitemporal diameter, and length and width of both the mesencephalon and cerebellum. A least squares line was fitted to the set of data points corresponding to each brain axis measured, and a t test verified that a linear model was an appropriate representation of the data. Based on these linear measurements it can be concluded that for forebrain grows more rapidly than the rest of the brain at the onset of tubular brain enlargement. Furthermore, as seen by comparing growth along two dimensions, the forebrain and midbrain grow at the same rate, whereas the cerebellum grows at different rates along the length and height axes. In addition, the cerebellum begins to grow later than the rostral part of the brain. Covariance analysis of the data points of the embryonic brain axes with data points of identical brain axes of the fetus showed that the measurements from the embryonic and fetal brain axes cannot be represented by a single regression line.

Anthropometry↗

The first appearance of the human nervous system at stage 8.

Eleven embryos of stage 8 (18 days), including a set of twins, were studied in detail and graphic reconstructions were prepared. This is the first report based on more than two specimens, as well as the first account of embryos of excellent histological quality at this developmental stage. Detailed measurements of the embryos are provided. It is found that the neural groove, which is the first morphological manifestation of the nervous system, is present in one quarter of embryos of stage 8. The neural folds are very largely cerebral rather than spinal. Correlations with other developmental features suggest that the neural groove is seen only when a certain degree of size and maturity has been reached by embryos of this important stage.

Anthropometry↗

[Introduction to the study of embryonic stages in man].

The internationally accepted Carnegie system of 23 developmental stages for the embryonic period proper (the first 8 post-ovulatory weeks) is outlined. At the end of this period the human embryo measures about 30 mm in C.-R. length. Some common misusages are noted, e.g., arabic numerals should be used for the states and the term "horizon" is obsolete; embryonic length is not a stage; STREETER's ages were based on the macaque and do not apply to the human. The introduction includes a discussion of the Carnegie Embryological Collection, the embryonic period, developmental stages, and finally a guide to embryonic staging in the human. An atlas of photographs of external views of embryos at the various Carnegie states is provided. Stages 1 to 8 (the presomite period, up to about 18 days) are described briefly and illustrated with photographs and photomicrographs. Stages 9 to 12 (the somitic period, about 20 to 26 days) and stages 13 to 23 (the postsomitic period, 4 to 8 post-ovulatory weeks) are summarized with reference to both external and internal development, and illustrated with photographs of the external appearances. In addition to (A) certain references cited in the introduction and in the text, the bibliography includes : (B) an annotated list of general works on staged human embryos, (C) an annotated list of selected examples of stages 1 to 15, and (D) an annotated list of references to information concerning staged embryos arranged according to the various systems of the body.

Bibliographies as Topic↗

Fine structure and myelination of the developing human vagus nerve.

The development of the cervical part of the vagus nerve was studied by electron microscopy in 17 human embryos and fetuses from 18 to 220 mm crown-rump (CR) length, approximately 7--23 postovulatory weeks old. By the end of the embryonic period proper, processes of neurolemmocytes are beginning to invade the nerve bundles of the vagus. Early in the fetal period, the nerve fibres become more regularly arranged, the lemmocyte/axon ratio is diminishing, the neurolemmocytes are dividing, and the connective tissue elements are becoming differentiated. By 14 postovulatory weeks (120 mm CR), examples of a 1:1 lemmocyte/axon ratio are observed, and the spiral development characteristic of myelination is beginning. By 17 weeks, myelinated fibres at varying phases of myelinogenesis are apparent, and desmosome-like junctions in the opposed plasma membranes are seen where lemmocyte processes form a mesaxon. By 23 postovulatory weeks, the diameter of the axons varies from 0.2 to 3.5 micrometer, and the vagus shows its mature structure, although nerve fibres at the beginning of myelin formation are still visible.

Desmosomes↗

The early development of the nervous system in staged insectivore and primate embryos.

The early development of the nervous system was studied in stage embryos of hemicentetes semispinosus, Microcebus murinus, Alouatta seniculus, Cebus appella, Cebus albifrons, macaca mulatta, and Homo sapiens. The specimens were assigned to Carnegie stages 11-13. Serial transverse sections were examined and graphic reconstructions were prepared. The early development of the neural tube is basically similar in all the species investigated but differences in detail are noticeable. The mesencephalic flexure serves in all cases as a landmark for malpighi's tripartite subdivision of the brain. The nonhuman embryos seem to show a little more variation than the human in the closure of the neuropores in relation to somitic count. With the exception of the later-appearing terminal-vomeronasal component, all major portions of the neural crest as classified by O'Rahilly ('65) are represented in both the nonhuman and the human embryos studied. No crest is present at the level of rhombomere 1, nor at rhombomere 3 except in the platyrrhines and some human embryos, nor at rhombomere 5 except in certain human specimens. An indication of the division of the trigeminal ganglion into its primary divisions is rare at stage 11 (C. apella), may be visible at stage 12 (Alouatta, macaca, Homo), and is definite (in Homo) at stage 13. Ganglionic contributions from head ectoderm (epipharyngeal placodes), as previously described in the human and some other vertebrate embryos, were sought and found in Cebus apella. In both nonhuman and human, a tendency is noted whereby the rostral limit of the occipitospinal crest, high at stage 11, seems to descend relatively at stage 12, and ascend again at stage 13 (at least in the human) to become associated with the appearance of the accessory and hypoglossal nerves. In general, the motor components of the nerves are identifiable before the sensory elements, and, in the present study, nerve fibers were first observed in the human at stage 13 in some of the cranial nerves and in the ventral roots of the spinal nerves.

Animals↗

The human chondrocranium at the end of the embryonic period, proper, with particular reference to the nervous system.

The chondrocranium at stage 23 (27-32 mm C.-R., 8 postovulatory weeks) was studied in detail to fill the descriptive gap between 7 and 9 weeks. Serial sections of ten embryos, all belonging to the same developmental stage, were investigated and compared. Graphic and Perspektomat reconstructions were made from three embryos. The chondrocranium forms a continuous mass of well-formed cartilage, which blends with early cartilage in the nasal, orbital, and otic regions, around the future foramen rotundum, and at the site of the parietal lamina. The chondrocranium and "membrane" bones cover a relatively small portion of the brain, namely 1) the medulla and pons, 2) the caudal half of the lateral portion of the cerebellar primordium, and 3) the rostroventral part of the cerebral hemispheres. The relationships of the cranial nerves were are also investigated. The degree of cranial development is intermediate between that at stage 20 (21 mm) studied by Lewis (the only other skull so far studied adequately in a staged embryo) and that of fetuses of 40 and 43 mm investigated by Macklin. On the whole, the resemblances to the fetal skulls are greater: ossification is beginning in the tectum posterius (to form the supraoccipital), and most of the "membrane" bones (except the parietal, tympanic, lacrimal, and nasal) show osseous areas. The foramen rotundum is present. The lower angle between the chordal and prechordal parts of the basal stem ranges from 129 degrees (which resembles that at stage 20, namely 122 degrees) to 115 degrees (which is the same as that at 40-43 mm). An orbito-parietal commissure is not yet present. The lower border of the larynx is at the level of the lower border of the fourth cervical vertebra. In the larynx, the thyroid laminae have usually not fused, the hyoid cartilage possesses greater and lesser cornua, the cricoid cartilage displays its signet-ring form, and the arytenoids are identifiable as condensed mesenchyme with some early cartilage. The cartilage of the first pharyngeal arches is covered in its ventral three-fourths by an osseous mandibular plate. Morphological variations within stage 23 are minor and appeared not to be related closely to each other, so that it was not possible to arrange the embryos in a linear developmental series based on their level of cranial morphogenesis.

Brain↗