The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes and proximal ribs of the vertebral column

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2259-2267 ◽  
Author(s):  
M. Leitges ◽  
L. Neidhardt ◽  
B. Haenig ◽  
B.G. Herrmann ◽  
A. Kispert
Keyword(s):  
Transcription Factor ◽  
Vertebral Column ◽  
Cell Mass ◽  
Homeobox Gene ◽  
Mesenchymal Cell ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Medial Part ◽  
Targeted Mutation ◽  
Vertebral Bodies

The axial skeleton develops from the sclerotome, a mesenchymal cell mass derived from the ventral halves of the somites, segmentally repeated units located on either side of the neural tube. Cells from the medial part of the sclerotome form the axial perichondral tube, which gives rise to vertebral bodies and intervertebral discs; the lateral regions of the sclerotome will form the vertebral arches and ribs. Mesenchymal sclerotome cells condense and differentiate into chondrocytes to form a cartilaginous pre-skeleton that is later replaced by bone tissue. Uncx4.1 is a paired type homeodomain transcription factor expressed in a dynamic pattern in the somite and sclerotome. Here we show that mice homozygous for a targeted mutation of the Uncx4.1 gene die perinatally and exhibit severe malformations of the axial skeleton. Pedicles, transverse processes and proximal ribs, elements derived from the lateral sclerotome, are lacking along the entire length of the vertebral column. The mesenchymal anlagen for these elements are formed initially, but condensation and chondrogenesis do not occur. Hence, Uncx4.1 is required for the maintenance and differentiation of particular elements of the axial skeleton.

Pax1 and Pax9 synergistically regulate vertebral column development

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5399-5408 ◽  
Author(s):  
H. Peters ◽  
B. Wilm ◽  
N. Sakai ◽  
K. Imai ◽  
R. Maas ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vertebral Column ◽  
Cell Lineage ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Potential Interaction ◽  
Specific Cell ◽  
Gradual Loss ◽  
Vertebral Bodies

The paralogous genes Pax1 and Pax9 constitute one group within the vertebrate Pax gene family. They encode closely related transcription factors and are expressed in similar patterns during mouse embryogenesis, suggesting that Pax1 and Pax9 act in similar developmental pathways. We have recently shown that mice homozygous for a defined Pax1 null allele exhibit morphological abnormalities of the axial skeleton, which is not affected in homozygous Pax9 mutants. To investigate a potential interaction of the two genes, we analysed Pax1/Pax9 double mutant mice. These mutants completely lack the medial derivatives of the sclerotomes, the vertebral bodies, intervertebral discs and the proximal parts of the ribs. This phenotype is much more severe than that of Pax1 single homozygous mutants. In contrast, the neural arches, which are derived from the lateral regions of the sclerotomes, are formed. The analysis of Pax9 expression in compound mutants indicates that both spatial expansion and upregulation of Pax9 expression account for its compensatory function during sclerotome development in the absence of Pax1. In Pax1/Pax9 double homozygous mutants, formation and anteroposterior polarity of sclerotomes, as well as induction of a chondrocyte-specific cell lineage, appear normal. However, instead of a segmental arrangement of vertebrae and intervertebral disc anlagen, a loose mesenchyme surrounding the notochord is formed. The gradual loss of Sox9 and Collagen II expression in this mesenchyme indicates that the sclerotomes are prevented from undergoing chondrogenesis. The first detectable defect is a low rate of cell proliferation in the ventromedial regions of the sclerotomes after sclerotome formation but before mesenchymal condensation normally occurs. At later stages, an increased number of cells undergoing apoptosis further reduces the area normally forming vertebrae and intervertebral discs. Our results reveal functional redundancy between Pax1 and Pax9 during vertebral column development and identify an early role of Pax1 and Pax9 in the control of cell proliferation during early sclerotome development. In addition, our data indicate that the development of medial and lateral elements of vertebrae is regulated by distinct genetic pathways.

Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2251-2258 ◽  
Author(s):  
A. Mansouri ◽  
A.K. Voss ◽  
T. Thomas ◽  
Y. Yokota ◽  
P. Gruss
Keyword(s):  
Cell Adhesion ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Homeobox Gene ◽  
Axial Skeleton ◽  
Adhesion Properties ◽  
Marker Analysis ◽  
Targeted Mutation ◽  
Differential Cell

The expression of the homeobox gene Uncx4.1 in the somite is restricted to the caudal half of the newly formed somite and sclerotome. Here we show that mice with a targeted mutation of the Uncx4.1 gene exhibit defects in the axial skeleton and ribs. In the absence of Uncx4.1, pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. Histological and marker analysis revealed that Uncx4.1 is not necessary for somite segmentation. It is required to maintain the condensation of the caudal half-sclerotome, from which the missing skeletal elements are derived. The loss of proximal ribs in Pax1/Pax9 double mutants and the data presented here argue for a role of Uncx4.1 upstream of Pax9 in the caudolateral sclerotome. Our results further indicate that Uncx4.1 may be involved in the differential cell adhesion properties of the somite.

The locomotor system

2013 ◽  
Author(s):  
Martin E. Atkinson
Keyword(s):  
Vertebral Column ◽  
Cervical Vertebrae ◽  
Lumbar Vertebrae ◽  
Posterior Wall ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Central Canal ◽  
The Body ◽  
Thoracic Vertebrae ◽  
Locomotor System

The locomotor system comprises the skeleton, composed principally of bone and cartilage, the joints between them, and the muscles which move bones at joints. The skeleton forms a supporting framework for the body and provides the levers to which the muscles are attached to produce movement of parts of the body in relation to each other or movement of the body as a whole in relation to its environment. The skeleton also plays a crucial role in the protection of internal organs. The skeleton is shown in outline in Figure 2.1A. The skull, vertebral column, and ribs together constitute the axial skeleton. This forms, as its name implies, the axis of the body. The skull houses and protects the brain and the eyes and ears; the anatomy of the skull is absolutely fundamental to the understanding of the structure of the head and is covered in detail in Section 4. The vertebral column surrounds and protects the spinal cord which is enclosed in the spinal canal formed by a large central canal in each vertebra. The vertebral column is formed from 33 individual bones although some of these become fused together. The vertebral column and its component bones are shown from the side in Figure 2.1B. There are seven cervical vertebrae in the neck, twelve thoracic vertebrae in the posterior wall of the thorax, five lumbar vertebrae in the small of the back, five fused sacral vertebrae in the pelvis, and four coccygeal vertebrae—the vestigial remnants of a tail. Intervertebral discs separate individual vertebrae from each other and act as a cushion between the adjacent bones; the discs are absent from the fused sacral vertebrae. The cervical vertebrae are small and very mobile, allowing an extensive range of neck movements and hence changes in head position. The first two cervical vertebrae, the atlas and axis, have unusual shapes and specialized joints that allow nodding and shaking movements of the head on the neck. The thoracic vertebrae are relatively immobile. combination of thoracic vertebral column, ribs, and sternum form the thoracic cage that protects the thoracic organs, the heart, and lungs and is intimately involved in ventilation (breathing).

Expression and function of Pax 1 during development of the pectoral girdle

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2773-2785 ◽  
Author(s):  
P.M. Timmons ◽  
J. Wallin ◽  
P.W. Rigby ◽  
R. Balling
Keyword(s):  
Gene Family ◽  
Functional Significance ◽  
Vertebral Column ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Appendicular Skeleton ◽  
Pectoral Girdle ◽  
Phenotypic Analysis ◽  
Developmental Abnormalities ◽  
And Function

Pax 1 is a member of the paired-box containing gene family. Expression has previously been observed in the developing sclerotomes and later in the anlagen of the intervertebral discs. Analysis of Pax 1-deficient undulated mice revealed an important role for this gene in the development of the axial skeleton, in which Pax 1 apparently functions as a mediator of notochordal signals during sclerotome differentiation. Here we demonstrate that Pax 1 is also transiently expressed in the developing limb buds. A comparative phenotypic analysis of different undulated alleles shows that this expression is of functional significance. In mice that are mutant for the Pax 1 gene severe developmental abnormalities are found in the pectoral girdle. These include fusions of skeletal elements which would normally remain separate, and failures in the differentiation of blastemas into cartilaginous structures. Although Pax 1 is also expressed in the developing hindlimb buds and Wolffian ridge, no malformations could be detected in the corresponding regions of Pax 1 mutant mice. These findings show that, in addition to its role in the developing vertebral column, Pax 1 has an important function in the development of parts of the appendicular skeleton.

A deep learning system for automated, multi-modality 2D segmentation of vertebral bodies and intervertebral discs

Bone ◽  
2021 ◽  
pp. 115972
Author(s):  
Abhinav Suri ◽  
Brandon C. Jones ◽  
Grace Ng ◽  
Nancy Anabaraonye ◽  
Patrick Beyrer ◽  
...  
Keyword(s):  
Deep Learning ◽  
Intervertebral Discs ◽  
Learning System ◽  
Vertebral Bodies

scholarly journals NEUROD1 Is Required for the Early α and β Endocrine Differentiation in the Pancreas

2021 ◽  
Vol 22 (13) ◽  
pp. 6713
Author(s):  
Romana Bohuslavova ◽  
Ondrej Smolik ◽  
Jessica Malfatti ◽  
Zuzana Berkova ◽  
Zaneta Novakova ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Cell Mass ◽  
Neonatal Diabetes ◽  
Diabetes Research ◽  
Pancreas Development ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Islet Cell ◽  
Endocrine Differentiation

Diabetes is a metabolic disease that involves the death or dysfunction of the insulin-secreting β cells in the pancreas. Consequently, most diabetes research is aimed at understanding the molecular and cellular bases of pancreatic development, islet formation, β-cell survival, and insulin secretion. Complex interactions of signaling pathways and transcription factor networks regulate the specification, growth, and differentiation of cell types in the developing pancreas. Many of the same regulators continue to modulate gene expression and cell fate of the adult pancreas. The transcription factor NEUROD1 is essential for the maturation of β cells and the expansion of the pancreatic islet cell mass. Mutations of the Neurod1 gene cause diabetes in humans and mice. However, the different aspects of the requirement of NEUROD1 for pancreas development are not fully understood. In this study, we investigated the role of NEUROD1 during the primary and secondary transitions of mouse pancreas development. We determined that the elimination of Neurod1 impairs the expression of key transcription factors for α- and β-cell differentiation, β-cell proliferation, insulin production, and islets of Langerhans formation. These findings demonstrate that the Neurod1 deletion altered the properties of α and β endocrine cells, resulting in severe neonatal diabetes, and thus, NEUROD1 is required for proper activation of the transcriptional network and differentiation of functional α and β cells.

scholarly journals Minimally invasive debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis: a long‐term follow‐up study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jianbiao Xu ◽  
Leiming Zhang ◽  
Rongqiang Bu ◽  
Yankang Liu ◽  
Kai-Uwe Lewandrowski ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Clinical Manifestations ◽  
Operation Time ◽  
Intervertebral Discs ◽  
Intraoperative Ct ◽  
Long Term Follow Up ◽  
Invasive Method ◽  
Vertebral Bodies ◽  
Adjacent Segments

Abstract Background Spondylodiscitis is an unusual infectious disease, which usually originates as a pathogenic infection of intervertebral discs and then spreads to neighboring vertebral bodies. The objective of this study is to evaluate percutaneous debridement and drainage using intraoperative CT-Guide in multilevel spondylodiscitis. Methods From January 2002 to May 2017, 23 patients with multilevel spondylodiscitis were treated with minimally invasive debridement and drainage procedures in our department. The clinical manifestations, evolution, and minimally invasive debridement and drainage treatment of this refractory vertebral infection were investigated. Results Of the enrolled patients, the operation time ranged from 30 minutes to 124 minutes every level with an average of 48 minutes. Intraoperative hemorrhage was minimal. The postoperative follow-up period ranged from 12 months to 6.5 years with an average of 3.7 years. There was no reactivation of infection in the treated vertebral segment during follow-up, but two patients with fungal spinal infection continued to progress by affecting adjacent segments prior to final resolution. According to the classification system of Macnab, one patient had a good outcome at the final follow-up, and the rest were excellent. Conclusions Minimally invasive percutaneous debridement and irrigation using intraoperative CT-Guide is an effective minimally invasive method for the treatment of multilevel spondylodiscitis.

scholarly journals The homeodomain-containing transcription factor X-nkx-5.1 inhibits expression of the homeobox gene Xanf-1 during the Xenopus laevis forebrain development

2004 ◽  
Vol 121 (12) ◽  
pp. 1425-1441 ◽  
Author(s):  
Andrey V. Bayramov ◽  
Natalia Yu. Martynova ◽  
Fedor M. Eroshkin ◽  
Galina V. Ermakova ◽  
Andrey G. Zaraisky
Keyword(s):  
Transcription Factor ◽  
Xenopus Laevis ◽  
Homeobox Gene ◽  
Factor X ◽  
Forebrain Development

scholarly journals Natural Orifice Translumenal Endoscopic Surgery for Anterior Spinal Procedures

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Priscilla Magno ◽  
Mouen A. Khashab ◽  
Manuel Mas ◽  
Samuel A. Giday ◽  
Jonathan M. Buscaglia ◽  
...  
Keyword(s):  
Thoracic Spine ◽  
Endoscopic Surgery ◽  
Vertebral Column ◽  
Bone Biopsy ◽  
Posterior Mediastinum ◽  
Direct Access ◽  
Thoracic Vertebrae ◽  
Natural Orifice ◽  
Vertebral Bone ◽  
Vertebral Bodies

Background. NOTES techniques allow transesophageal access to the mediastinum. The aim of this study was to assess the feasibility of transesophageal biopsy of thoracic vertebrae.Methods. Nonsurvival experiments on four 50-kg porcine animals were performed. Transesophageal access to the mediastinum was attained using submucosal tunneling technique.Results. The posterior mediastinum was successfully accessed and navigated in all animals. Vertebral bodies and intervertebral spaces were easily approached while avoiding damage to adjacent vessels. Bone biopsy was successfully performed without complications, but the hardness of bone tissue resulted in small and fragmented samples.Conclusions. Peroral transesophageal access into the posterior mediastinum and thoracic vertebral bone biopsy was feasible and safe. The proximity of the esophagus to the vertebral column provides close and direct access to the thoracic spine and opens up new ground for the performance of multilevel anterior spine procedures using NOTES techniques.

scholarly journals Pyogenic and tuberculous discitis: magnetic resonance imaging findings for differential diagnosis

2013 ◽  
Vol 46 (3) ◽  
pp. 173-177 ◽  
Author(s):  
Cristiano Gonzaga de Souza ◽  
Emerson Leandro Gasparetto ◽  
Edson Marchiori ◽  
Paulo Roberto Valle Bahia
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Correct Diagnosis ◽  
Cord Compression ◽  
Intervertebral Discs ◽  
University Hospital ◽  
Imaging Findings ◽  
Resonance Imaging ◽  
Radiographic Findings ◽  
Vertebral Bodies

Spondylodiscitis represents 2%–4% of all bone infections cases. The correct diagnosis and appropriate treatment can prevent complications such as vertebral collapse and spinal cord compression, avoiding surgical procedures. The diagnosis is based on characteristic clinical and radiographic findings and confirmed by blood culture and biopsy of the disc or the vertebra. The present study was developed with Clementino Fraga Filho University Hospital patients with histopathologically and microbiologically confirmed diagnosis of spondylodiscitis, submitted to magnetic resonance imaging of the affected regions. In most cases, pyogenic spondylodiscitis affects the lumbar spine. The following findings are suggestive of the diagnosis: segmental involvement; ill-defined abscesses; early intervertebral disc involvement; homogeneous vertebral bodies and intervertebral discs involvement. Tuberculous spondylodiscitis affects preferentially the thoracic spine. Most suggestive signs include: presence of well-defined and thin-walled abscess; multisegmental, subligamentous involvement; heterogeneous involvement of vertebral bodies; and relative sparing of intervertebral discs. The present pictorial essay is aimed at showing the main magnetic resonance imaging findings of pyogenic and tuberculous discitis.

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