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.

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.

scholarly journals The Polycomb group protein MEDEA controls cell proliferation and embryonic patterning in Arabidopsis

2020 ◽  
Author(s):  
Sara Simonini ◽  
Marian Bemer ◽  
Stefano Bencivenga ◽  
Valeria Gagliardini ◽  
Nuno D. Pires ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lineage ◽  
Embryonic Cell ◽  
The Body ◽  
Polycomb Group ◽  
Normal Embryo ◽  
Embryonic Patterning ◽  
Polycomb Group Protein ◽  
Group Protein

Establishing the body plan of a multicellular organism relies on precisely orchestrated cell divisions coupled with pattern formation. In animals, cell proliferation and embryonic patterning are regulated by Polycomb group (PcG) proteins that form various multisubunit complexes (Grossniklaus and Paro, 2014). The evolutionary conserved Polycomb Repressive Complex 2 (PRC2) trimethylates histone H3 at lysine 27 (H3K27me3) and comes in different flavors in the model plant Arabidopsis thaliana (Förderer et al., 2016; Grossniklaus and Paro, 2014). The histone methyltransferase MEDEA (MEA) is part of the FERTILIZATION INDEPENDENT SEED (FIS)-PRC2 required for seed development4. Although embryos derived from mea mutant egg cells show morphological abnormalities (Grossniklaus et al., 1998), defects in the development of the placenta-like endosperm are considered the main cause of seed abortion (Kinoshita et al., 1999; Scott et al., 1998), and a role of FIS-PRC2 in embryonic patterning was dismissed (Bouyer et al., 2011; Leroy et al., 2007). Here, we demonstrate that endosperm lacking MEA activity sustains normal embryo development and that embryos derived from mea mutant eggs abort even in presence of a wild-type endosperm because MEA is required for embryonic patterning and cell lineage determination. We show that, similar to PcG proteins in mammals, MEA regulates embryonic growth by repressing the transcription of core cell cycle components. Our work demonstrates that Arabidopsis embryogenesis is under epigenetic control of maternally expressed PcG proteins, revealing that PRC2 was independently recruited to control embryonic cell proliferation and patterning in animals and plants.

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).

The role of Pax-1 in axial skeleton development

Development ◽  
1994 ◽  
Vol 120 (5) ◽  
pp. 1109-1121 ◽  
Author(s):  
J. Wallin ◽  
J. Wilting ◽  
H. Koseki ◽  
R. Fritsch ◽  
B. Christ ◽  
...  
Keyword(s):  
Proximal Part ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Paraxial Mesoderm ◽  
Single Amino Acid ◽  
Lumbar Region ◽  
Entire Axis ◽  
Mouse Mutants ◽  
Column Formation

Previous studies have identified a single amino-acid substitution in the transcriptional regulator Pax-1 as the cause of the mouse skeletal mutant undulated (un). To evaluate the role of Pax-1 in the formation of the axial skeleton we have studied Pax-1 protein expression in early sclerotome cells and during subsequent embryonic development, and we have characterized the phenotype of three different Pax-1 mouse mutants, un, undulated-extensive (unex) and Undulated short-tail (Uns). In the Uns mutation the whole Pax-1 locus is deleted, resulting in the complete absence of Pax-1 protein in these mice. The other two genotypes are interpreted as hypomorphs. We conclude that Pax-1 is necessary for normal vertebral column formation along the entire axis, although the severity of the phenotype is strongest in the lumbar region and the tail. Pax-1-deficient mice lack vertebral bodies and intervertebral discs. The proximal part of the ribs and the rib homologues are also missing or severely malformed, whereas neural arches are nearly normal. Pax-1 is thus required for the development of the ventral parts of vertebrae. Embryonic analyses reveal that although sclerotomes are formed in mutant embryos, abnormalities can be detected from day 10.5 p.c. onwards. The phenotypic analyses also suggest that the notochord still influences vertebral body formation some days after the sclerotomes are formed. Furthermore, the notochord diameter is larger in mutant embryos from day 12 p.c., due to increased cell proliferation. In the strongly affected genotypes the notochord persists as a rod-like structure and the nucleus pulposus is never properly formed. Since the notochord is Pax-1-negative these findings suggest a bidirectional interaction between notochord and paraxial mesoderm. The availability of these Pax-1 mutant alleles permitted us to define an early role for Pax-1 in sclerotome patterning as well as a late role in intervertebral disc development. Our observations suggest that Pax-1 function is required for essential steps in ventral sclerotome differentiation, i.e. for the transition from the mesenchymal stage to the onset of chondrogenesis.

scholarly journals hox gene expression predicts tetrapod-like axial regionalization in the skate, Leucoraja erinacea

2021 ◽  
Vol 118 (51) ◽  
pp. e2114563118
Author(s):  
Katharine E. Criswell ◽  
Lucy E. Roberts ◽  
Eve T. Koo ◽  
Jason J. Head ◽  
J. Andrew Gillis
Keyword(s):  
Gene Expression ◽  
Vertebral Column ◽  
Evolutionary History ◽  
Cell Lineage ◽  
Axial Skeleton ◽  
Lineage Tracing ◽  
Paraxial Mesoderm ◽  
Evolutionary Transition ◽  
Geometric Morphometric ◽  
Geometric Morphometric Analysis

The axial skeleton of tetrapods is organized into distinct anteroposterior regions of the vertebral column (cervical, trunk, sacral, and caudal), and transitions between these regions are determined by colinear anterior expression boundaries of Hox5/6, -9, -10, and -11 paralogy group genes within embryonic paraxial mesoderm. Fishes, conversely, exhibit little in the way of discrete axial regionalization, and this has led to scenarios of an origin of Hox-mediated axial skeletal complexity with the evolutionary transition to land in tetrapods. Here, combining geometric morphometric analysis of vertebral column morphology with cell lineage tracing of hox gene expression boundaries in developing embryos, we recover evidence of at least five distinct regions in the vertebral skeleton of a cartilaginous fish, the little skate (Leucoraja erinacea). We find that skate embryos exhibit tetrapod-like anteroposterior nesting of hox gene expression in their paraxial mesoderm, and we show that anterior expression boundaries of hox5/6, hox9, hox10, and hox11 paralogy group genes predict regional transitions in the differentiated skate axial skeleton. Our findings suggest that hox-based axial skeletal regionalization did not originate with tetrapods but rather has a much deeper evolutionary history than was previously appreciated.

scholarly journals Multidimensional Chromatin Regulation of Cell Lineage Differentiation in a Metazoan Embryo

2020 ◽  
Author(s):  
Zhiguang Zhao ◽  
Rong Fan ◽  
Weina Xu ◽  
Yangyang Wang ◽  
Xuehua Ma ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Single Cell Analysis ◽  
Cell Lineage ◽  
Specific Cell ◽  
Chromatin Regulation ◽  
Chromatin Dynamics ◽  
Critical Dimensions ◽  
C Elegans ◽  
Lineage Differentiation

SUMMARYHow chromatin dictates cell differentiation is an intriguing question in developmental biology. Here, a reporter gene integrated throughout the genome was used as a sensor to map the chromatin activity landscape in lineage-resolved cells during C. elegans embryogenesis. Single-cell analysis of chromatin dynamics across critical dimensions of cell differentiation was performed, including lineage, tissue, and symmetry. During lineage progression, chromatin gradually diversifies in general and exhibits switch-like changes following specific cell division, which is predictive of anterior-posterior fate asymmetry. Upon tissue differentiation, chromatin of cells from distinct lineages converge to tissue-specific states but retain “memory” of each cell’s lineage history, which contributes to intra-tissue heterogeneity. However, cells with a morphologically left-right symmetric organization utilize a predetermination chromatin strategy to program analogous regulatory states in early progenitor cells. Additionally, chromatin co-regulation drives the functional coordination of the genome. Collectively, this work reveals the role of multidimensional chromatin regulation in cell differentiation.

scholarly journals Yap/Taz-TEAD ACTIVITY LINKS MECHANICAL CUES TO CELL PROGENITOR BEHAVIOR DURING HINDBRAIN SEGMENTATION

2018 ◽  
Author(s):  
Adrià Voltes ◽  
Covadonga F Hevia ◽  
Chaitanya Dingare ◽  
Simone Calzolari ◽  
Javier Terriente ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Tissue Growth ◽  
Specific Cell ◽  
Cell Behaviors ◽  
Mechanical Signals ◽  
Matrix Cell ◽  
Physical Cues

SUMMARYCells perceive their microenvironment through chemical and physical cues. However, how mechanical signals are interpreted during embryonic tissue deformation resulting in specific cell behaviors is largely unexplored. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, cell shape and actomyosin cytoskeleton. In this work, we unveiled the role of Yap/Taz-TEAD activity as sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during hindbrain compartmentalization. Monitoring in vivo Yap/Taz-activity during hindbrain segmentation we discovered that boundary cells respond to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decrease their proliferative activity when Yap/Taz-TEAD ceased, preceding changes of cell fate: from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining the progenitor features in the hindbrain boundary cell population.

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.

scholarly journals SPONDYLODISCITIS DIAGNOSTICS IN NOWADAYS: BASIC CT AND MRI SIGNS

2019 ◽  
pp. 39-47
Author(s):  
A. S. Vinokurov ◽  
O. I. Belenkaya ◽  
A. L. Yudin ◽  
A. V. Kim
Keyword(s):  
Surgical Treatment ◽  
Intervertebral Discs ◽  
Early Diagnostics ◽  
Canal Stenosis ◽  
Vertebral Bodies ◽  
Mri Study ◽  
Methodological Aspects ◽  
Ct And Mri

For many reasons spondylodiscitis (SDC) is a complicated pathology. It is caused by difficulty in early diagnostics, the need for surgical treatment (including repeated interventions), long term and high cost of antibiotic therapy. Objective. The goal is to identify and describe the main CT and MRI symptoms of SDC, to assess their frequency and specificity. The next aim is to note the peculiarities of the radiologist’s practice with such patients. Materials and methods. We studied the data of 25 patients with proved SDC, and we analyzed CT and MRI symptoms (both common and rare), and the role of contrast enhancement (СE) in both methods and important clinical and laboratory aspects. Results.The infiltration of vertebral bodies and intervertebral discs were the most frequent SDC signs, abscesses also were very common. The most significant type of abscess was epidural which led to the formation of vertebral canal stenosis and  to neurological deficit. The important methodological aspects of the MRI study were noted to improve its quality. Conclusion. We recommend performing both CT and MRI, if possible, for all patients with SDC because of the different diagnostic tasks that are important for clinicians.CE significantly increases the MRI informativity.

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