Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection.

Afadin, a scaffold protein controlling the activity of the nectin family of cell adhesion molecules, regulates important morphogenetic processes during development. In the central nervous system, afadin has critical roles in neuronal migration, axonal elongation, and synapse formation. Here we examine the role of afadin in development of spinal motor circuits. Afadin elimination in motor neuron progenitors results in striking locomotor behavior: left-right limb alternation is substituted by synchronous activation, characteristic of bound gait. We find that afadin function at the neuroepithelium is required for structural organization of the spinal midline and central canal morphogenesis. Perturbation of afadin results in formation of two central canals, aberrant contralateral wiring of different classes of spinal premotor interneurons, and loss of left-right limb alternation, highlighting important developmental principles controlling the assembly of spinal motor circuits.

Normal development of the fetal spinal canal and spinal cord at T12 on 3.0-T MRI.

BACKGROUND: The studies that described the dimensions of the normal fetal thoracic spinal canal and spinal cord on magnetic resonance imaging (MRI) are scarce. PURPOSE: To determine the normal appearance of the fetal spinal canal and spinal cord at T12 across different gestational ages using 3.0-T MRI. MATERIAL AND METHODS: The spines of 43 normal human fetuses, aged 15-40 weeks, were scanned by 3.0-T MRI. All specimens were scanned using a GE 3.0-T MRI scanner. Imaging of the T12 vertebrae was performed in the coronal, sagittal, and axial planes. The anterior-posterior (AP) diameter, width, and cross-sectional area of the spinal canal and spinal cord at T12 were measured. The influence of gestational age on these parameters was investigated with a scatter plot and linear regression analysis using Pearson correlation coefficient. RESULTS: The normal morphology of the fetal vertebra at T12 can be clearly showed by MRI; the spinal canal appeared circular, while the spinal cord was ellipsoid. Linear regression analysis showed a significant positive correlation between the AP diameter, width, and cross-sectional area of the spinal canal at T12 and gestational age. CONCLUSION: Postmortem MRI is a reliable method for understanding the growth dynamics of the spinal canal and spinal cord at T12. Findings from this study would benefit the prenatal diagnosis of congenital malformations by MRI.

Morphometric changes in the spinal cord during prenatal life: a stereological study in sheep.

This study describes the volumetric changes in the spinal cord during prenatal life in sheep using quantitative stereological methods. Twenty healthy sheep fetuses were included in the present study, divided into four groups representing 9-11, 12-14, 15-17, and 18-20 weeks of gestation. In each group, the spinal cord was dissected out and sampled according to the unbiased systematic random sampling method then used for stereological estimations. The total volume of spinal cord, volume of gray matter (GM), volume of white matter (WM), ratio of GM volume to WM volume, and volume of central canal (CC) were estimated in the whole spinal cord and its various regions using Cavalieri's principle. The total volume of the spinal cord increased 8 times from week 9 to week 20. The cervical region showed the greatest (9.7 times) and the sacral region the least (6.3 times) volumetric change. The CC volume of the whole spinal cord increased 5.8 times from week 9 to week 20. The cervical region developed faster (8.2 times) and the thoracic region slower (4.4 times) than the total spinal cord. During development, the volume ratio of GM to WM decreased from lower toward upper regions. The greatest volume changes occurred mostly in weeks 9-11 and 12-14. The cervical region showed the greatest volume changes in comparison with other regions of the spinal cord.

Role of radial glia in transformation of the primitive lumen to the central canal in the developing rat spinal cord.

In the last quarter of the embryonic development of rat and shortly after a termination of neurogenesis, the transformation of the spinal cord primitive lumen (pL) to the central canal (CC) occurs. In this work, we show that this phenomenon is not an insignificant event but it is directly associated with the processes of gliogenesis. Using a light microscopy and immunohistochemistry, we monitored the development of the rat embryonic spinal cord from the end of the neurogenesis on the embryonic day 17 until the maturation of the spinal cord during the first postnatal weeks. Our observations demonstrate the importance of the transformation of the pL to the CC and its connection with gliogenesis, and the mechanism of this transformation is proposed. It is found that a segregation of the glutamate transporter (GLAST) immunopositive cells from the alar plates and transformation of the radial glial cells to the fibrous and protoplasmic astrocytes play presumably a key role in the diminution of the ventricular zone. Results indicate that the very transformation and migration of the radial glial cells during gliogenesis could result in a transformation of the pL to the CC.

The structure and development of avian lumbosacral specializations of the vertebral canal and the spinal cord with special reference to a possible function as a sense organ of equilibrium.

The avian lumbosacral vertebral column and spinal cord show a number of specializations which have recently been interpreted as a sense organ of equilibrium. This sense organ is thought to support balanced walking on the ground. Although most of the peculiar structures have been described previously, there was a need to reevaluate the specializations with regard to the possible function as a sense organ. Specializations were studied in detail in the adult pigeon. The development of the system was studied both in the pigeon (semiprecocial at hatching) and in the chicken (precocial). Specializations in the vertebral canal consist of a considerable enlargement, which is not due to an increase in the size of the spinal nervous tissue, but to a large glycogen body embedded in a dorsal rhomboid sinus. The dorsal wall of the vertebral canal shows segmented bilateral dorsal grooves, which are covered by the meninges towards the lumen of the vertebral canal leaving openings in the midline and laterally. This results in a system of lumbosacral canals which look and may function similar to the semicircular canals in the inner ear. Laterally these canals open above ventrolateral protrusions or accessory lobes of the spinal cord which contain neurons. There are large subarachnoidal cerebrospinal fluid spaces, lateral and ventral to the accessory lobes. Movement of this fluid is thought to stimulate the lobes mechanically. As to the development of avian lumbosacral specializations, main attention was given to the organization of the lobes and the adjacent fluid spaces including the dorsal canals. In the pigeon the system is far from being adult-like at hatching but maturates rapidly after hatching. In the chicken the system looks already adult-like at hatching. The implications derived from the structural findings are discussed with regard to a possible function of the lumbosacral specializations as a sense organ of equilibrium. The adult-like organization in the newly hatched chickens, which walk around immediately after hatching, supports the assumed function as a sense organ involved in the control of locomotion on the ground.

Development of the posterior neural tube in human embryos.

Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.

Three-dimensional sonographic evaluation of the fetal lumbar spinal canal.

In a prospective cross-sectional ultrasound study the size of the fetal lumbar spinal canal was evaluated to determine reference values for the lumbar part of the vertebral canal. One hundred and sixty-seven pregnant women undergoing routine obstetric ultrasound were studied between 16 and 41 weeks of gestation. Exclusion criteria consisted of structural fetal anomalies or growth restriction. Area and volume of the vertebral canal at L1, L3 and L5 were calculated by three-dimensional (3D) ultrasound. Length of the lumbar spine was also determined. The size of the spinal canal and spinal length correlated well with gestational age. No gestational-age-dependent differences in area and volume measurements between upper and lower lumbar spine were found. The results provide an in vivo assessment of the spinal canal by 3D ultrasound over the entire gestation period.

The fetal spinal canal--a three-dimensional study.

The size of the lumbar spinal canal was evaluated in a prospective cross-sectional ultrasound (US) study to determine normal size values for lumbar part of the vertebral canal. A total of 88 patients undergoing routine obstetric US were studied between 16-41 weeks gestation. Structural anomalies or growth restriction were excluded. Area and volume of the vertebral canal in L1, L3 and L5 were calculated by three-dimensional (3-D) US. The size of the spinal canal correlated well with gestational age and no major differences could be found between upper and lower lumbar spine. By 3-D US, in vivo assessment of the spinal canal becomes possible. Further studies are needed to confirm our findings.

The Henderson Trust Lecture. The development of the vertebral canal and associated neuro-physiological abnormalities.

In this lecture I have attempted to demonstrate that the size of the lumbar vertebral canal has clinical importance. The canal develops very early in life, and impaired growth at this time affects other growing systems. The patient with spinal stenosis has more than a spinal disadvantage. Improved obstetric and childhood care has the potential not only to prevent some of the troublesome back problems, but also to influence the health and neurological status in adult life. I hope that the first Henderson Trustees would have been encouraged by this lecture. It supports some of the philosophy that stimulated an interest in Phrenology. In the lumbar spine at least, the container-the vertebral canal-seems to have an important relationship to the function of its neurological contents.

Development of the lumbar and sacral vertebral canal in utero.

STUDY DESIGN: This study analyzed the development of the lumosacral vertebral canal and dural sac in human fetus. A collection of fetuses and embryos was used to assess the development of different parameters of the spinal canal. OBJECTIVES: The data were analyzed for the dynamics of the development and also compared with mean adult spinal parameters. SUMMARY OF BACKGROUND DATA: Transversely sectioned specimens and nonsectioned specimens free of abnormalities were selected from the Boyd Collection of human embryos and fetuses. METHODS: The sections were photographed alongside a micrometric scale, and the nonsectioned specimens were scanned by magnetic resonance imaging. The films were computer analyzed for spinal and dural parameters. The error of the measurements was assessed. RESULTS: The most rapid growth period of the spinal canal parameters is between 18-36 weeks' gestation. After 30 weeks of intrauterine life, the upper lumbar canal grows faster than the lower lumbar region. The distal end of the dural sac begins to rise from S5 after 14 weeks. CONCLUSIONS: At the end of intrauterine growth, the interpedicular diameter of the spinal canal from L1 to L4 is 70% of the adult size, however, at L5, the canal is only 50% mature at birth. Therefore, if there is growth impairment in early infancy, the upper lumbar region is partially protected in contrast with the L5 level.

[Correlations in the development of the spinal cord, dura mater and spinal canal in humans]. / Sopriazhennost' razvitiia spinnogo mozga, ego tverdoi obolochki i pozvonochnogo kanala cheloveka.

The spinal cord axial structures (AS) (its dura mater and vertebral canal) demonstrate the greatest growth rate during the intrauterine period and on the 18th month. After birth for the dura mater this age is 3 years, and for the spinal cord and the vertebral canal--7 years of age. The pubertal jump in growth of these formations is noted during the adolescent age (17-21 years). During the first two decades AS demonstrate asymptotic type of growth. In AS development the following periods in common have been revealed: a) intensive growth in children up to 7 years of age; b) growth stabilization (from 8 up to 16 years of age); c) period of a relative morphological stability (22-35 years); d) period of unstable compensatory-adaptive rearrangements (36-60 years); e) period of involutive changes (61-90 years).

[Developmental characteristics of the human lumbar spinal column at various periods of ontogeny]. / Osobennosti razvitiia poiasnichnogo otdela pozvonochnogo stolba cheloveka v razlivhnye periody ontogeneza.

Regularities in development and differentiation of vertebrae have been investigated according to ageing. The data concerning the size of the vertebral canal at the level of the lumbar vertebral bodies and intervertebral discs, intensity of increase of these dimensions in various age periods, the character of spatial relations of sizes and form of the canal has been analysed. The transversal section area of the canal and the body in the corresponding segment varies between 1:3 and 1:5.5. By means of x-ray osteophotometry the mineralization degree of the lumbar vertebral bodies has been determined in men of various age. An important fact has been stated on a close connection between mineral saturation in juvenile and first mature ages with induces of general strength.

[Structure and dynamics of the size of the epidural space in human fetuses and newborn infants]. / Stroenie i dunamika razmerov épidura'lnogo prostranstva u plodov cheloveka i novorozhdennykh.

Basing on our definition of the ES as a complex of peridural anatomical formations and taking into account certain peculiarities of their topographic distribution, 4 areas (anterior, posterior and two lateral) are defined. The posterior area of the ES by its sizes predominates over all the others. The ES value is determined by differences in rates of size increment of the vertebral canal and in rates of size increment of the spinal cord dura mater (SCDM). Position of the SCDM sac concerning the central axis of the canal predetermines++ the size of the ES four areas. The dimensions of the ES areas are not similar at various levels of the spinal column. For example, the dimensions of the ES posterior area in newborns are the greatest in the cervical part at CVII, in the thoracic--at ThIV-VII, in the lumbar--at LI-III, and the dimensions of the ES anterior area--at CVII, ThI-IV, LIV-V and Sr. The lateral ES areas are the widest at CI, ThIII, LV and SI. The greatest increase in the rate of increment of linear sizes and area is observed for the spinal canal and spinal cord in 5-, 8- and 9-month-old fetuses and for SCDM--in 5- and 8-month-old fetuses and for ES--in 6-, 8- and 9-month-old fetuses. The topographic peculiarities in the ES structure revealed and rearrangement of its dimensions in the fetuses and newborns can be useful in interpretation of problems on functional formation of the vertebral column, spinal cord and its tunics, and be of applied aspect at various manipulations performed in these formations in premature infants and in newborns.

Descriptive studies of occlusion and reopening of the spinal canal of the early chick embryo.

Occlusion and reopening of the lumen of the spinal cord, two processes believed to be involved in early brain enlargement, were examined in chick embryos to determine what morphological features characterize these events. Occlusion begins at a particular craniocaudal level near the time that the neural folds become apposed in the dorsal midline and blocklike somites form from the segmental plates. During occlusion, the apical sides of the lateral walls of the neural tube are in close apposition. Interdigitating apical surface protrusions, cross-luminal intercellular junctions, and abundant cell-surface materials are lacking. Reopening has occurred by about stage 20 throughout most of the craniocaudal extent of the spinal cord. A lumen suddenly appears during this process, but correlated structural changes that might account for such a dramatic change in morphology were undetectable. Reopening involves the release of the forces that previously maintained occlusion, or the generation of new forces that overcome those causing occlusion, but what these forces are remains to be determined. Observations suggest that forces generated outside of the neural tube might be largely responsible for occlusion, and experiments are in progress to test this possibility.

Sacrococcygeal developmental abnormalities and tumors in children.

Lesions from the SC region of children examined histologically at the RAHC were: 1. Malformations almost always associated with spina bifida aperta or occulta: 183 myelomeningocele (MM), 32 meningocele (M), 35 lipoMM and lipoma, 19 dermoid cyst, six occult meningocele, two Pacinian hamartoma, one short filum, four hindgut cysts or sinuses, two tailgut cysts, and two epithelial heterotopia. 2. Neoplasms, usually without spina bifida: 56 teratomas (11 malignant), five ependymomas (two purely subcutaneous), and 14 miscellaneous primary malignancies, (most neuroblastoma and rhabdomyosarcoma). Distinction between MM with glial tissue and M without glial tissue is important as M had a much better prognosis, less than a third developing hydrocephalus, and 77% walking unaided. Of those with glial tissue, the eight without Arnold-Chiari malformation were myelocystocele associated with cloacal exstrophy (six), caudal regression syndrome (one), and microcephaly (one). Postsacral glial tissue without paraplegia may occur with a subcutaneous vestige of filum terminale, or with herniation of the nonfunctioning half of a diplomyelia. Of postsacral "lipomas" and dermoids, 70% had an intraspinal connection through an occult spina bifida. This posterior vertebral defect is easily overlooked as the arches normally may not ossify until after 6 years. Therefore, the pathologist receiving a postsacral specimen may wish to alert the clinician to the high incidence of late effects from an occult intraspinal component or tethering of the spinal cord. Transsacral hindgut herniations and cysts probably result from ectoendodermal adhesions. Presacral multicystic malformations with mixed squamous and mucus cell lining are probably tailgut remnants or anorectal duplications, and may be mistaken for dermoid or teratoma. In SC teratoma in infants, contrary to some reports on ovarian teratoma in adults, immature tissues do not indicate a worse prognosis. Malignancy is virtually confined to teratomas including a carcinomatous or "yolk sac" component. It is more common in predominantly presacral examples and rare before the age of 4 months. SC ependymoma differs from ependymoma elsewhere in that it may be primary outside the craniospinal cavity (presacral or postsacral), may have a myxopapillary pattern special to the region, and although low-grade and slow growing, is more likely to metastasize beyond the central nervous system. Postsacral examples arise from vestiges of the filum terminale which are normal in the subcutis there. Combinations of all these lesions occur with vertebral defects and with each other.(ABSTRACT TRUNCATED AT 400 WORDS)

An electron microscopic study of the development of the ependyma of the central canal of the mouse spinal cord.

The central canal of the adult mouse spinal cord is lined for most of its extent by ependymal cells which are rich in microfilaments and whose apical surface is covered with matted, broad microvilli. The canal itself is filled with amorphous material containing glycogen granules. Two forms of this material are present, a dark form rich in glycogen, and a light form containing a few glycogen granules. Each type appears to be surrounded by a membrane. The upper cervical region, however, has a large empty lumen and the ependymal cells in this region have only scattered, narrow microvilli. During development, the floor and roof plates are at first composed largely of ependymoglial cells, unlike the lateral walls, where undifferentiated neuroepithelial cells predominate. By E15 few undifferentiated neuroepithelial cells remain. At E17 the morphology of the ependymal cells changes. Their apical surface becomes covered with matted, club-shaped microvilli and the central canal is filled with glycogen-containing material. By P5 microfibrils are present in large bundles in the ependymal cells. The piaglial surface opposite the roof and floor plates has finger-like projections unique to these regions and these persist at the surface of the dorsal median septum until myelination is well advanced after P5. The fibres forming the dorsal median septum are at first pale processes containing scattered glycogen granules and microtubules. By P5 microfibrils are present and at P150 the processes are packed with masses of microfibrils.

[Arguments in favor of the genetic origin of malformed syringohydromyelic pictures]. / Arguments en faveur de l'origine génétique des tableaux malformatifs syringohydromyéliques.

After a critical analysis of the criteria usually used for arguing in favor of the hydrodynamic determinism of the syringohydromyelic malformations, the authors report convincing data according to which such dysmorphic status would be the result of abnormalities in the genetic programs of the morphogenesis of the central canal.