scholarly journals TGFβ signaling is required for sclerotome resegmentation during development of the spinal column in Gallus gallus.

2021 ◽  
Author(s):  
Sade W Clayton ◽  
Ronisha McCardell ◽  
Rosa Serra
Keyword(s):  
Direct Evidence ◽  
Spinal Column ◽  
Axial Skeleton ◽  
Gallus Gallus ◽  
Intervertebral Discs ◽  
Lineage Tracing ◽  
Chick Embryos ◽  
Fluorescent Tracers ◽  
Tgfβ Signaling

We previously showed the importance of TGFβ signaling in development of the mouse axial skeleton. Here, we provide the first direct evidence that TGFβ signaling is required for resegmentation of the sclerotome using chick embryos. Lipophilic fluorescent tracers, DiO and DiD, were microinjected into adjacent somites of embryos treated with or without TGFβR1 inhibitor, SB431542, at developmental day E2.5 (HH16). Lineage tracing of labeled cells was observed over the course of 4 days until the completion of resegmentation at E6.5 (HH32). Vertebrae were malformed and intervertebral discs were small and misshapen in SB431542 injected embryos. Inhibition of TGFβ signaling resulted in alterations in resegmentation that ranged between full, partial, and slanted shifts in distribution of DiO or DiD labeled cells within vertebrae. Patterning of rostro- caudal markers within sclerotome was disrupted at E3.5 after treatment with SB431542 with rostral domains expressing both rostral and caudal markers. Hypaxial myofibers were also increased in thickness after treatment with the inhibitor. We propose that TGFβ signaling regulates rostro-caudal polarity and subsequent resegmentation in sclerotome during spinal column development.

scholarly journals Loss of potassium from embryonic chick hearts in potassium-free media with and without calcium

1938 ◽  
Vol 124 (837) ◽  
pp. 446-450
Keyword(s):  
Phosphate Buffer ◽  
Direct Evidence ◽  
Watch Glass ◽  
Chick Embryos ◽  
Embryonic Chick ◽  
Intercellular Spaces ◽  
Experimental Solution ◽  
Free Media ◽  
And Control ◽  
Day By Day

Experiments already described (Murray 1938) led to the inference that the cells of the chick embryonic heart lose potassium in potassium-free media. The experiments here described provide direct evidence of this. The hearts were dissected out of 2 ½-3 day chick embryos and placed in the solution PC (Table I) until they had started to beat. They were then thoroughly washed, and were allowed to lie for 5 min. (2 min. in Exp. 1) in the last wash. This last wash is called control A. The solutions used for washing were from the same flasks as the experimental solution. After their passage through control A the hearts were transferred to 2 c.c. of the experimental solution in a Jena watch-glass. After various times in this the hearts were discarded and both the experimental solution and control A were collected. If the experiment extended over more than 1 day the experimental solution and control A were used over again day by day until all the hearts in the experiment had passed through them. The use of control A was necessary for two reasons: ( a ) to show that potassium was not still being washed out of the intercellular spaces at the end of washing ( b ) in experiments lasting over several days the washing solution was fresh each day, but the experimental solution was of course not changed. Hence any small amount of potassium being carried over from the last wash would accumulate in the experimental solution because of the daily increment and might seriously affect the result; but by leaving the hearts for several minutes in the last wash (control A) and by not changing it for fresh on successive days, any such increase would be detected in that solution. In addition to control A, a daily sample (control B) was taken from the same flasks as the solutions used for washing. Details of the solutions are given in Table I ; a phosphate buffer was always used.

A single morphogenetic field gives rise to two retina primordia under the influence of the prechordal plate

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 603-615 ◽  
Author(s):  
H. Li ◽  
C. Tierney ◽  
L. Wen ◽  
J.Y. Wu ◽  
Y. Rao
Keyword(s):  
Expression Pattern ◽  
Lineage Tracing ◽  
Chick Embryos ◽  
Median Region ◽  
Prechordal Plate ◽  
Prechordal Mesoderm ◽  
New Gene ◽  
Vertebrate Embryos ◽  
Migration Of Cells ◽  
Anterior Neural Plate

Two bilaterally symmetric eyes arise from the anterior neural plate in vertebrate embryos. An interesting question is whether both eyes share a common developmental origin or they originate separately. We report here that the expression pattern of a new gene ET reveals that there is a single retina field which resolves into two separate primordia, a suggestion supported by the expression pattern of the Xenopus Pax-6 gene. Lineage tracing experiments demonstrate that retina field resolution is not due to migration of cells in the median region to the lateral parts of the field. Removal of the prechordal mesoderm led to formation of a single retina both in chick embryos and in Xenopus explants. Transplantation experiments in chick embryos indicate that the prechordal plate is able to suppress Pax-6 expression. Our results provide direct evidence for the existence of a single retina field, indicate that the retina field is resolved by suppression of retina formation in the median region of the field, and demonstrate that the prechordal plate plays a primary signaling role in retina field resolution.

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.

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).

scholarly journals Single cell lineage tracing reveals a role for TgfβR2 in intestinal stem cell dynamics and differentiation

2016 ◽  
Vol 113 (43) ◽  
pp. 12192-12197 ◽  
Author(s):  
Jared M. Fischer ◽  
Peter P. Calabrese ◽  
Ashleigh J. Miller ◽  
Nina M. Muñoz ◽  
William M. Grady ◽  
...  
Keyword(s):  
Single Cell ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Cell Lineage ◽  
Transforming Growth Factor Β ◽  
Lineage Tracing ◽  
Secretory Cells ◽  
Cancer Tissue ◽  
Tgfβ Signaling

Intestinal stem cells (ISCs) are maintained by a niche mechanism, in which multiple ISCs undergo differential fates where a single ISC clone ultimately occupies the niche. Importantly, mutations continually accumulate within ISCs creating a potential competitive niche environment. Here we use single cell lineage tracing following stochastic transforming growth factor β receptor 2 (TgfβR2) mutation to show cell autonomous effects of TgfβR2 loss on ISC clonal dynamics and differentiation. Specifically, TgfβR2 mutation in ISCs increased clone survival while lengthening times to monoclonality, suggesting that Tgfβ signaling controls both ISC clone extinction and expansion, independent of proliferation. In addition, TgfβR2 loss in vivo reduced crypt fission, irradiation-induced crypt regeneration, and differentiation toward Paneth cells. Finally, altered Tgfβ signaling in cultured mouse and human enteroids supports further the in vivo data and reveals a critical role for Tgfβ signaling in generating precursor secretory cells. Overall, our data reveal a key role for Tgfβ signaling in regulating ISCs clonal dynamics and differentiation, with implications for cancer, tissue regeneration, and inflammation.

scholarly journals Tgfβ signaling is required for tenocyte recruitment and functional neonatal tendon regeneration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Deepak A Kaji ◽  
Kristen L Howell ◽  
Zerina Balic ◽  
Dirk Hubmacher ◽  
Alice H Huang
Keyword(s):  
Functional Role ◽  
Gene Deletion ◽  
Tendon Injuries ◽  
Lineage Tracing ◽  
Loss Of Function ◽  
Tgfβ Signaling ◽  
Cell Recruitment ◽  
Tendon Regeneration ◽  
Targeted Gene Deletion ◽  
Small Molecule Inhibition

Tendon injuries are common with poor healing potential. The paucity of therapies for tendon injuries is due to our limited understanding of the cells and molecular pathways that drive tendon regeneration. Using a mouse model of neonatal tendon regeneration, we identified TGFβ signaling as a major molecular pathway that drives neonatal tendon regeneration. Through targeted gene deletion, small molecule inhibition, and lineage tracing, we elucidated TGFβ-dependent and TGFβ-independent mechanisms underlying tendon regeneration. Importantly, functional recovery depended on canonical TGFβ signaling and loss of function is due to impaired tenogenic cell recruitment from both Scleraxis-lineage and non-Scleraxis-lineage sources. We show that TGFβ signaling is directly required in neonatal tenocytes for recruitment and that TGFβ ligand is positively regulated in tendons. Collectively, these results show a functional role for canonical TGFβ signaling in tendon regeneration and offer new insights toward the divergent cellular activities that distinguish regenerative vs fibrotic healing.

scholarly journals Intervertebral disc homeostasis at normal conditions and during pathology

2012 ◽  
Vol 93 (2) ◽  
pp. 304-307
Author(s):  
A E Kobyzev
Keyword(s):  
Intervertebral Disc ◽  
Metabolic Disorders ◽  
Spinal Column ◽  
Intervertebral Discs ◽  
Metabolic Processes ◽  
Functional Changes ◽  
Normal Metabolism ◽  
Capillary Zone ◽  
Vertebral Bodies ◽  
Complex Structural

Intervertebral discs are rather complex structural units of the spine. It is believed that a disturbance of the factors of their homeostasis immediately leads to changes in the bone tissue of the vertebral bodies and, consequently, to pathological changes at the level of the vertebral-motor segment. It follows that the maintenance of normal metabolism within the discs is one of the key directions in the prevention of many clinically important lesions involving the entire vertebral complex. The causes of metabolic processes disorders in the intervertebral disc can be divided into several levels: chronic diseases that directly affect the blood supply to the spinal column as a whole; diseases that affect the permeability of the capillary zone of the subchondral zone of the vertebral bodies; disturbances in the delivery of nutrients into the disc through its matrix, which serves an important selective barrier. However, regardless of the level of the causes of metabolic disorders, all of which eventually lead to anatomical and functional changes in the intervertebral discs and to their subsequent incapacity to provide the daily life cycle of the vertebral complex, consisting of periods of stress and relaxation. Thus, based on the known literature data we can conclude that: the intervertebral discs to date, remain poorly understood elements, however even from a narrow range of studies on this subject it is evident that their functionality is largely dependent on the properties of the disc matrix and the interstitial nature of metabolic processes.

Treatment: spinal surgery

2016 ◽  
Author(s):  
Heinrich Boehm ◽  
Y. Raja Rampersaud
Keyword(s):  
Axial Spondyloarthritis ◽  
Treatment Options ◽  
Spinal Column ◽  
Intervertebral Discs ◽  
Minor Trauma ◽  
Normal Stresses ◽  
Muscle Action ◽  
Associated Symptoms ◽  
Spinal Ligaments ◽  
Remarkable Progress

Despite remarkable progress in understanding the pathological processes and alleviating symptoms by TNFα‎ blocking medication, the mechanism that converts flexible tissue into bone still cannot be completely prevented or reversed. In axial spondyloarthritis, components of motion segments, such as zygoapophyseal joints, intervertebral discs, and spinal ligaments, can ossify in varying sequence, extent, and location between the ilium and occiput. Throughout this process, the spinal column is vulnerable to kyphotic deformity due to gravity, body weight, muscle action, and life’s flexion-based activities. Areas with low fusion tendency, such as atlanto-axial joints, and post-traumatically weakened spots of formerly ankylosed vertebral block (Andersson’s lesion) can endanger the spinal cord by instability, dislocation, and compression, from what is typically minor trauma or simple repetitive, but otherwise normal, stresses. Once functionally significant deformity or presence of instability and associated symptoms are established, conservative treatment options are lacking and surgical consideration is required.

scholarly journals Reciprocal Regulation of TRPS1 and miR-221 in Intervertebral Disc Cells

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1170 ◽  
Author(s):  
Letizia Penolazzi ◽  
Elisabetta Lambertini ◽  
Leticia Scussel Bergamin ◽  
Carlotta Gandini ◽  
Antonio Musio ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Underlying Mechanism ◽  
Axial Skeleton ◽  
Intervertebral Discs ◽  
Tissue Samples ◽  
Reciprocal Regulation ◽  
Gene Reporter Assay ◽  
Innovative Therapies ◽  
Disc Cells ◽  
High Level

Intervertebral disc (IVD), a moderately moving joint located between the vertebrae, has a limited capacity for self-repair, and treating injured intervertebral discs remains a major challenge. The development of innovative therapies to reverse IVD degeneration relies primarily on the discovery of key molecules that, occupying critical points of regulatory mechanisms, can be proposed as potential intradiscal injectable biological agents. This study aimed to elucidate the underlying mechanism of the reciprocal regulation of two genes differently involved in IVD homeostasis, the miR-221 microRNA and the TRPS1 transcription factor. Human lumbar IVD tissue samples and IVD primary cells were used to specifically evaluate gene expression and perform functional analysis including the luciferase gene reporter assay, chromatin immunoprecipitation, cell transfection with hTRPS1 overexpression vector and antagomiR-221. A high-level expression of TRPS1 was significantly associated with a lower pathological stage, and TRPS1 overexpression strongly decreased miR-221 expression, while increasing the chondrogenic phenotype and markers of antioxidant defense and stemness. Additionally, TRPS1 was able to repress miR-221 expression by associating with its promoter and miR-221 negatively control TRPS1 expression by targeting the TRPS1-3′UTR gene. As a whole, these results suggest that, in IVD cells, a double-negative feedback loop between a potent chondrogenic differentiation suppressor (miR-221) and a regulator of axial skeleton development (TRPS1) exists. Our hypothesis is that the hostile degenerated IVD microenvironment may be counteracted by regenerative/reparative strategies aimed at maintaining or stimulating high levels of TRPS1 expression through inhibition of one of its negative regulators such as miR-221.

scholarly journals TGFβ signaling is required for tenocyte recruitment and functional neonatal tendon regeneration

2019 ◽  
Author(s):  
Deepak A. Kaji ◽  
Kristen L. Howell ◽  
Alice H. Huang
Keyword(s):  
Gene Deletion ◽  
Tendon Injuries ◽  
Lineage Tracing ◽  
Loss Of Function ◽  
Tgfβ Signaling ◽  
Major Pathway ◽  
Cell Recruitment ◽  
Tendon Regeneration ◽  
Targeted Gene Deletion ◽  
Small Molecule Inhibition

ABSTRACTTendon injuries are common with poor healing potential. The paucity of therapies for tendon is due to our limited understanding of the cells and molecules that drive tendon regeneration. Using a model of neonatal mouse tendon regeneration, we determined the molecular basis for regeneration and identify TGFβ signaling as a major pathway. Through targeted gene deletion, small molecule inhibition, and lineage tracing, we elucidated TGFβ-dependent and –independent mechanisms underyling tendon regeneration. Importantly, functional recovery depended on TGFβ signaling and loss of function is due to impaired tenogenic cell recruitment from bothScxlinand non-Scxlinsources. We show that TGFβ signaling is required directly in neonatal tenocytes for recruitment and that TGFβ is positively regulated in tendons. Collectively, these results are the first to show a functional role for TGFβ signaling in tendon regeneration and offer new insights toward the divergent cellular activities that may lead to regenerative vs fibrotic healing.

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