Talk:Musculoskeletal System - Axial Skeleton Development

From Embryology
Revision as of 02:06, 16 March 2011 by S8600021 (talk | contribs) (→‎2002)

2010

Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc

BMC Dev Biol. 2010 Mar 9;10:29.

Sohn P, Cox M, Chen D, Serra R.

Department of Cell Biology, University of Alabama at Birmingham, Birmingham AL, USA.

Abstract BACKGROUND: Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-beta superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing mouse tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-beta has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-beta action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing mouse IVD and to begin to understand the mechanism of TGF-beta action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing mouse vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice as well as in sclerotome cultures treated with TGF-beta or BMP4.

RESULTS: Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We also generated lists of genes regulated by TGF-beta or BMP4 in cultured sclerotome. As expected, treatment with BMP4 resulted in up-regulation of cartilage marker genes including Acan, Sox 5, Sox6, and Sox9. In contrast, treatment with TGF-beta1 did not regulate expression of cartilage markers but instead resulted in up-regulation of many IVD markers including Fmod and Adamtsl2.

CONCLUSIONS: We propose TGF-beta has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-beta that warrant further investigation as regulators of IVD development.

PMID: 20214815

http://www.ncbi.nlm.nih.gov/pubmed/20214815

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848151

http://www.biomedcentral.com/1471-213X/10/29

2007

Altered axial skeletal development

Birth Defects Res B Dev Reprod Toxicol. 2007 Dec;80(6):451-72.

Tyl RW, Chernoff N, Rogers JM. Center for Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA. rwt@rti.org

Abstract The axial skeleton is routinely examined in standard developmental toxicity bioassays and has proven to be sensitive to a wide variety of chemical agents. Dysmorphogenesis in the skull, vertebral column and ribs has been described in both human populations and in laboratory animals used to assess potential adverse developmental effects. This article emphasizes vertebrae and rib anomalies both spontaneous and agent induced. Topics discussed include the morphology of the more common effects; incidences in both human and experimental animal populations; the types of anomalies induced in the axial skeleton by methanol, boric acid, valproic acid and others; the postnatal persistence of common skeletal anomalies; and the genetic control of the development of the axial skeleton. Tables of the spontaneous incidence of axial anomalies in both humans and animals are provided.


PMID: 18157900

2006

Normal fetal lumbar spine on postmortem MR imaging

AJNR Am J Neuroradiol. 2006 Mar;27(3):553-9.

Widjaja E, Whitby EH, Paley MN, Griffiths PD.

Academic Section of Radiology, University of Sheffield, Sheffield, United Kingdom. Abstract BACKGROUND AND PURPOSE: There is an increasing interest in use of postmortem MR imaging as an adjunct or alternative to autopsy. Before evaluating spinal pathology on postmortem MR imaging, it is important to have knowledge of the normal appearance of the fetal spine at different gestational ages. The aim of this study is to describe the MR imaging appearances of normal development of the fetal spine at different gestational ages.

METHODS: Postmortem MR imaging was performed on 30 fetuses ranging from 14 to 41 gestational weeks. There was no structural abnormality of the spine in these fetuses on MR imaging or at autopsy. Fast spin-echo T2-weighted MR imaging of the lumbar spine was performed in the coronal plane in all cases and supplemented by sagittal and/or axial imaging. The following parameters were measured: height of the L1/2 disk and L2 vertebral body and area of ossification center in L2 vertebral body as well as area of vertebral body. The signal intensity of the disk space and the vertebral level of conus termination were also assessed.

RESULTS: The height and area of the vertebral body increased linearly with gestational age (P <.01). The increase in disk space was proportionally greater than the increase in vertebral body height as gestational age increased (P <.01). The disk space appeared as a linear low-signal-intensity area in fetuses < or = 21 weeks gestation but increasingly developed high signal intensity in the disk after 21 weeks. The size of the ossification center increased with gestational age (P <.01), and the ratio of ossification center to the overall size of the vertebral body also increased with gestational age (P <.01). In fetuses less than 35 weeks of age, the conus lay between L2 and L5 level, whereas in fetuses more than 35 weeks of age, the conus lay between L1/2 and L2/3 level.

CONCLUSION: Understanding the normal growth and signal-intensity characteristics of the fetal spine on postmortem MR imaging is essential before studying abnormal fetal spine.

PMID: 16551992

2002

Three-dimensional sonographic evaluation of the fetal lumbar spinal canal

J Anat. 2002 May;200(5):439-43.

Wallny T, Schild RL, Fimmers R, Hansmann ME.

Department of Orthopaedics, University of Bonn, Germany. wallny@uni-bonn.de Abstract 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.

PMID: 12090390 http://www.ncbi.nlm.nih.gov/pubmed/12090390

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570700

2000

The development of the avian vertebral column

Anat Embryol (Berl). 2000 Sep;202(3):179-94.

Christ B, Huang R, Wilting J.

Institute of Anatomy, University of Freiburg, Germany. christb@uni-freiburg.de Abstract Segmentation of the paraxial mesoderm leads to somite formation. The underlying molecular mechanisms involve the oscillation of "clock-genes" like c-hairy-1 and lunatic fringe indicative of an implication of the Notch signaling pathway. The cranio-caudal polarity of each segment is already established in the cranial part of the segmental plate and accompanied by the expression of genes like Delta1, Mesp1, Mesp2, Ulicx-1, and EphA4 which are restricted to one half of the prospective somite. Dorsoventral compartmentalization of somites leads to the development of the dermomyotome and the sclerotome, the latter forming as a consequence of an epithelio-to-mesenchymal transition of the ventral part of the somite. The sclerotome cells express Pax-1 and Pax-9, which are induced by notochordal signals mediated by sonic hedgehog (Shh) and noggin. The craniocaudal somite compartmentalization that becomes visible in the sclerotomes is the prerequisite for the segmental pattern of the peripheral nervous system and the formation of the vertebrae and ribs, whose boundaries are shifted half a segment compared to the sclerotome boundaries. Sclerotome development is characterized by the formation of three subcompartments giving rise to different parts of the axial skeleton and ribs. The lateral sclerotome gives rise to the laminae and pedicles of the neural arches and to the ribs. Its development depends on signals from the notochord and the myotome. The ventral sclerotome giving rise to the vertebral bodies and intervertebral discs is made up of Pax-1 expressing cells that have invaded the perinotochordal space. The dorsal sclerotome is formed by cells that migrate from the dorso-medial angle of the sclerotome into the space between the roof plate of the neural tube and the dermis. These cells express the genes Msx1 and Msx2, which are induced by BMP-4 secreted from the roof plate, and they later form the dorsal part of the neural arch and the spinous process. The formation of the ventral and dorsal sclerotome requires directed migration of sclerotome cells. The regionalization of the paraxial mesoderm occurs by a combination of functionally Hox genes, the Hox code, and determines the segment identity. The development of the vertebral column is a consequence of a segment-specific balance between proliferation, apoptosis and differentiation of cells.

PMID: 10994991 http://www.ncbi.nlm.nih.gov/pubmed/10994991

1990

The human vertebral column at the end of the embryonic period proper. 4. The sacrococcygeal region

J Anat. 1990 Feb;168:95-111.

O'Rahilly R, Müller F, Meyer DB.

Department of Human Anatomy, University of California, Davis 95616. Abstract The sacral and coccygeal vertebrae at 8 postovulatory weeks (the end of the embryonic period proper) have been studied by means of graphic reconstructions. The cartilaginous sacrum is now a definitive unit composed of five separable vertebrae, each of which consists of a future centrum and bilateral neural processes. The base of each neural process consists of an anterolateral or alar element, not present in the lumbar region, and a posterolateral part, which includes costal and transverse elements. The usual illustrations, in which the costal component is placed in the alar element, are incorrect. The future dorsal foramina (containing dorsal rami) face laterally in the embryo and are in line with the thoracicolumbar intervertebral foramina. Considerable differential growth is required to change the dorsal openings from a lateral to a dorsal positions. The intervertebral foramina transmit ventral rami, but pelvic foramina are not yet present. The lumbosacral plexus is completed by S.N.1-3; S.N.4, 5 and Co.N.1 form the pelvic plexus. The inferior hypogastric plexus and the hypogastric nerves are present. The sacrum takes part in the spina bifida occulta that characterises the entire length of the embryonic vertebral column. The coccygeal vertebrae, which are variable, were 4-6 in number in the present series. The first is the best developed. The ventriculus terminalis ends usually at the level of Co.V.1 and the spinal cord generally at Co.V.5. The coccygeal notochord ends commonly in bifurcation or trifurcation. 'Haemal arches' were not observed.

PMID: 2182589 http://www.ncbi.nlm.nih.gov/pubmed/2182589

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1256893

The human vertebral column at the end of the embryonic period proper. 3. The thoracicolumbar region

J Anat. 1990 Feb;168:81-93.

O'Rahilly R, Müller F, Meyer DB.

Department of Human Anatomy, University of California, Davis 95616. Abstract The present study of the thoracicolumbar region continues an investigation of the vertebral column at 8 postovulartory weeks (the end of the embryonic period proper) by means of graphic reconstructions. The cartilaginous vertebrae have short neural processes associated with the normal spina bifida occulta present at this time. The separate cartilaginous centres that several authors believe to exist in the cervical and lumbar costal elements, but which have not been observed by the present authors, have been thought to be the forerunners of extrathoracic ribs. A distinction needs to be made, however, between such centres and ribs. Similarly, in the fetal period, ossific loci in the costal elements of CV 7 are very frequent, whereas cervical ribs in the adult are relatively rare. The neurocentral joints, and hence the boundaries between neural arches and centra, are unclear before ossification has begun and has progressed during the fetal period. The sternal bands are almost completely united and the scapula is high in position. Neural relationships aid in the determination of homologous parts within the vertebral column, but clarification of corresponding parts has not previously been possible within the embryonic period. Areas ventral to the dorsal rami are ribs in the thoracic region and costal elements in other regions. Areas underlying the dorsal rami are transverse processes in the thoracic region and minute 'true' transverse elements in the cervical and lumbar regions. Thus, the descriptive lumbar transverse processes correspond to the true transverse processes and the ribs in the thoracic region. The dorsal rami of the thoracic nerves pass between the transverse processes and the tubercles of the ribs and then divide. The ventral rami of lumbar Nerves 1 and 2 resemble the thoracic in their course, whereas those of Nerves 3-5 are similar to the sacral. The thoracic dorsal roots are sloping and, associated with the greater height of the lumbar centra, the lumbar roots even more so. The directions of the various dorsal roots reflect differences in growth gradients between vertebral column and spinal cord. The thoracic and lumbar portions of the column change little in proportion during the embryonic period proper.

PMID: 2323997 http://www.ncbi.nlm.nih.gov/pubmed/2323997

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1256892

1983

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

J Anat. 1983 Jan;136(Pt 1):181-95. O'Rahilly R, Müller F, Meyer DB.

Abstract 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.

PMID: 6833119 http://www.ncbi.nlm.nih.gov/pubmed/6833119

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171939

1980

The human vertebral column at the end of the embryonic period proper. 1. The column as a whole

J Anat. 1980 Oct;131(Pt 3):565-75.

O'Rahilly R, Muller F, Meyer DB.

Abstract The present investigation of the vertebral column at 8 post-ovulatory weeks, the first such study based on precise reconstructions, has revealed 33 or 34 cartilaginous vertebrae arranged in flexion and approximately 20--33 mm in total length. At the end of the embryonic period proper, a typical vertebra, such as TV6, consists of a centrum that is continuous with two neural processes. Pedicles, articular and transverse processes, but no spinous processes, are identifiable. The tips of the neural processes, which are formed by the laminae, are connected by fibrous tissue and resemble the condition of total rachischisis. The union of the laminae, the onset of ossification, and the appearance of articular cavities are characteristic of the early fetal period. The variations encountered within a single developmental stage were noted. They were mostly minor, e.g. the number of coccygeal elements and the extent of the dorsal growth of the neural processes.

PMID: 7216919 http://www.ncbi.nlm.nih.gov/pubmed/7216919


1979

A radiographic study of the human fetal spine. 3. Longitudinal growth

J Anat. 1979 Jun;128(Pt 4):777-87.

Bagnall KM, Harris PF, Jones PR.

Abstract Regression equations are presented which describe the growth in length of the various regions of the vertebral column in the human fetus. From 8 weeks on the thoracic is always the longest region and the sacral the shortest, while the lumbar region is longer than the cervical. From the regression equations predictions of fetal vertebral length can be made from fetal age: this should be useful in obstetric practice when diagnostic ultrasound techniques are being employed for the diagnosis of growth disorders and skeletal abnormalities. A different developmental pattern emerges when average 'vertebral units' for each region are compared. The lumbar vertebrae are always the largest with the thoracic, cervical and sacral vertebrae being progressively smaller.

PMID: 489466 http://www.ncbi.nlm.nih.gov/pubmed/489466

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1232880/

1975

The development of vertebral bone marrow of human fetuses

Blood. 1975 Sep;46(3):389-408.

Chen LT, Weiss L.

Abstract The development of the bone marrow of the thoracic vertebrae in seven human fetuses ranging from 95 to 150 mm in crown-rump length (CRL) was studied using light and electron microscopy. In the 95-mm CRL, hypertrophy of the chondrocytes occurred in the central region of the vertebrae, and blood vessels penetrated there from dorsal and ventral sides of the vertebral body. The primary marrow was represented by liberated cartilage lacunnae, occupied by the thin-walled blood vessels and a few mesenchymal cells and mononuclear cells containing granules or vacuoles (GMC). In the 99-mm CRL, chondroclasts were active in removing the cartilage near the central region of the vertebrae. Consequently, a large cavity was formed and occupied by a dilated sinus. GMC were numerous. Osteoblasts and osteocytes were increased in number. Reticular cells with long processes containing large amounts of glycogen began to appear in the extravascular space and formed the loosely arranged cellular meshwork of the hematopoietic compartment. Bundles of collagen fibrils were scattered in the meshwork. Hematopoietic cells were recognizable only in the 105-mm-CRL fetus and increased in number in the 120-mm-CRL fetus. The sinus endothelium was very thin and continuous without apertures except where blood cells crossed the wall. The developing blood cells lying against the outside of the sinus endothelium indented it. At points, collagen fibrils attached to the outside of endothelial cells and appeared to function as the anchoring filaments of lymphatics. The physiologic implications of the association of stromal cells, vascular sinuses, and hematopoietic cells are discussed in relationship to the microhematopoietic environment of the bone marrow.

PMID: 1097001