scholarly journals Altered bone growth dynamics prefigure craniosynostosis in a zebrafish model of Saethre-Chotzen syndrome

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Camilla S Teng ◽  
Man-chun Ting ◽  
D'Juan T Farmer ◽  
Mia Brockop ◽  
Robert E Maxson ◽  
...  
Keyword(s):  
Osteoblast Differentiation ◽  
Bone Growth ◽  
Growth Dynamics ◽  
Mouse Genetics ◽  
Cranial Sutures ◽  
Coronal Suture ◽  
Zebrafish Model ◽  
Parietal Bones ◽  
Progenitor Maintenance ◽  
Coronal Region

Cranial sutures separate the skull bones and house stem cells for bone growth and repair. In Saethre-Chotzen syndrome, mutations in TCF12 or TWIST1 ablate a specific suture, the coronal. This suture forms at a neural-crest/mesoderm interface in mammals and a mesoderm/mesoderm interface in zebrafish. Despite this difference, we show that combinatorial loss of TCF12 and TWIST1 homologs in zebrafish also results in specific loss of the coronal suture. Sequential bone staining reveals an initial, directional acceleration of bone production in the mutant skull, with subsequent localized stalling of bone growth prefiguring coronal suture loss. Mouse genetics further reveal requirements for Twist1 and Tcf12 in both the frontal and parietal bones for suture patency, and to maintain putative progenitors in the coronal region. These findings reveal conservation of coronal suture formation despite evolutionary shifts in embryonic origins, and suggest that the coronal suture might be especially susceptible to imbalances in progenitor maintenance and osteoblast differentiation.

Study on Morphometric Features of Coronal Suture Along with it Absence and Craniosynostosis

2021 ◽  
Vol 9 (4) ◽  
pp. 8151-8155
Author(s):  
Khaleel N ◽  
◽  
Angadi A V ◽  
Muralidhar P S ◽  
Shabiya M ◽  
...  
Keyword(s):  
Birth Defect ◽  
Cranial Sutures ◽  
Coronal Suture ◽  
Cranial Suture ◽  
Medical Sciences ◽  
Hot Climate ◽  
Morphometric Features ◽  
Metopic Suture ◽  
Parietal Bones ◽  
The Brain

Background: Cranial sutures are syndesmosis between the cranial bones. The coronal suture is oblique in direction and extends between the frontal and the parietal bones. Craniosynostosis is a rare birth defect that occurs when the coronal suture in the skull fuses prematurely, but the brain continues to grow and develop. This leads to a misshapen head. There are a number of forms of this defect, such as coronal, sagittal, lambdoid, and metopic. Materials and Methods: Total 500 skulls were used for study, coronal suture length measured by thread method, distance between Nasion to bregma and midsupraorbital rim to coronal suture were measured. For finding skull with absence of coronal, sagittal, lambdoid, and metopic suture, we examined many skulls during routine osteology classes of Medical, Dental and other medical sciences students. Around 500 skull observed and we find only one skull with absence of left coronal suture completely. Results: The length of coronal suture was 24.8+1.4cm length, the distance between nasion to bregma was 126.7 +10.25 mm and Midsupraorbital rim to cranial suture was 102.76+8.64mm We have found only one skull with absence of coronal suture. Some of the skulls shows partly fusion of sagittal, coronal sutures. The skull with complete absence of coronal suture showing the features of other sutures clearly and right side of coronal suture is showing the complete suture. The skull was not damaged and it is in perfect condition which was using by students for their osteology study. Conclusion: We found the skull with absence of left coronal suture, which may resulted due to craniosynostosis. It may be due to hot climate in India also might be resulted for absence of suture. KEY WORDS: Birth defect, Skull, Coronal suture, Craniosynostosis.

scholarly journals Author response: Altered bone growth dynamics prefigure craniosynostosis in a zebrafish model of Saethre-Chotzen syndrome

2018 ◽  
Author(s):  
Camilla S Teng ◽  
Man-chun Ting ◽  
D'Juan T Farmer ◽  
Mia Brockop ◽  
Robert E Maxson ◽  
...  
Keyword(s):  
Bone Growth ◽  
Growth Dynamics ◽  
Author Response ◽  
Zebrafish Model

scholarly journals Embryonic requirements forTcf12in the development of the mouse coronal suture

2021 ◽  
Author(s):  
Man-chun Ting ◽  
D’Juan T. Farmer ◽  
Camilla S. Teng ◽  
Jinzhi He ◽  
Yang Chai ◽  
...  
Keyword(s):  
Bone Growth ◽  
Parietal Bone ◽  
Compound Heterozygous ◽  
Asymmetric Distribution ◽  
Coronal Suture ◽  
Loss Of Function ◽  
Coronal Synostosis ◽  
The Individual ◽  
Parietal Bones ◽  
Hlh Transcription Factors

AbstractA major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in the basic HLH transcription factorsTWIST1andTCF12. While compound heterozygousTcf12; Twist1mice display severe coronal synostosis, the individual role ofTcf12has remained unexplored. Here we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement forTcf12in suture formation, as combined deletion ofTcf12in the embryonic neural crest and mesoderm, but not in the postnatal suture mesenchyme, disrupts the coronal suture. We also detect asymmetric distribution of Grem1 + mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. InTcf12mutants, reduced asymmetry correlates with lack of bone overlap. Our results indicate a largely embryonic function of Tcf12 in controlling the rate and asymmetrical growth of calvarial bones and establishment of suture boundaries, which together ensure the proper formation of the overlapping coronal suture.

scholarly journals Embryonic requirements for Tcf12 in the development of the mouse coronal suture

Development ◽  
2021 ◽  
Author(s):  
Man-chun Ting ◽  
D'Juan T. Farmer ◽  
Camilla S. Teng ◽  
Jinzhi He ◽  
Yang Chai ◽  
...  
Keyword(s):  
Bone Growth ◽  
Parietal Bone ◽  
Compound Heterozygous ◽  
Asymmetric Distribution ◽  
Coronal Suture ◽  
Loss Of Function ◽  
Coronal Synostosis ◽  
The Individual ◽  
Parietal Bones ◽  
Hlh Transcription Factors

A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the basic HLH transcription factors TWIST1 and TCF12. While compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detect asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.

scholarly journals A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis

2019 ◽  
Vol 28 (15) ◽  
pp. 2501-2513 ◽  
Author(s):  
Jacqueline A C Goos ◽  
Walter K Vogel ◽  
Hana Mlcochova ◽  
Christopher J Millard ◽  
Elahe Esfandiari ◽  
...  
Keyword(s):  
De Novo ◽  
Cranial Sutures ◽  
Coronal Suture ◽  
Nurd Complex ◽  
Binding Studies ◽  
Amino Terminal ◽  
Skull Vault ◽  
Order Of Magnitude ◽  
Transcriptional Complexes ◽  
Dynamics Simulations

Abstract Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4–MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4–MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency.

Compensatory growth following premature closure of the coronal suture in rabbits

1982 ◽  
Vol 57 (4) ◽  
pp. 535-542 ◽  
Author(s):  
William J. Babler ◽  
John A. Persing ◽  
H. Richard Winn ◽  
John A. Jane ◽  
George T. Rodeheaver
Keyword(s):  
Compensatory Growth ◽  
Cranial Sutures ◽  
Coronal Suture ◽  
Skull Morphology ◽  
Content Type ◽  
Premature Closure ◽  
New Zealand White Rabbits ◽  
Skull Growth ◽  
Skull Deformation ◽  
Surgical Release

✓ Premature closure of a cranial suture results in skull deformation characterized by inhibited skull growth in a direction perpendicular to the course of the affected suture. Early surgical release of the closed suture results in a “normal” skull morphology. The present experimental study measured alterations in growth at the transverse cranial sutures that occurred following induced premature closure of the coronal suture and its subsequent release in New Zealand White rabbits. Using roentgenocephalometric methods, growth and morphometric changes were monitored at the frontonasal, coronal, and anterior lambdoid sutures following premature closure of the coronal suture at 9 days of age. The results indicated that premature closure of the coronal suture did not result in compensatory (increased) growth at the other transverse sutures of the vault. In fact, growth at these sutures was significantly reduced. This reduced growth at adjacent transverse sutures was not ameliorated by early surgical release of the fused suture.

Bone Regulation of Insulin Secretion and Glucose Homeostasis

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
Patricia Ducy
Keyword(s):  
Cell Biology ◽  
Regulatory Networks ◽  
Bone Growth ◽  
Bone Cells ◽  
Protective Role ◽  
Brain Cell ◽  
Mouse Genetics ◽  
The Body ◽  
Lipocalin 2 ◽  
Inner Organs

Abstract For centuries our image of the skeleton has been one of an inert structure playing a supporting role for muscles and a protective role for inner organs like the brain. Cell biology and physiology modified this view in the 20st century by defining the constant interplay between bone-forming and bone resorbing cells that take place during bone growth and remodeling, therefore demonstrating that bone is as alive as any other tissues in the body. During the past 40 years human and, most important, mouse genetics, have allowed not only the refinement of this notion by identifying the many genes and regulatory networks responsible for the crosstalk existing between bone cells, but have redefined the role of bone by showing that its influence goes way beyond its own physiology. Among its newly identified functions is the regulation of energy metabolism by 2 bone-derived hormones, osteocalcin and lipocalin-2. Their biology and respective roles in this process are the topic of this review.

scholarly journals Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain)

2011 ◽  
Vol 7 (4) ◽  
pp. 593-596 ◽  
Author(s):  
Cayetana Martinez-Maza ◽  
Antonio Rosas ◽  
Samuel García-Vargas ◽  
Almudena Estalrrich ◽  
Marco de la Rasilla
Keyword(s):  
Morphological Traits ◽  
Bone Growth ◽  
Bone Remodelling ◽  
Histological Study ◽  
Growth Dynamics ◽  
Mental Foramen ◽  
Primate Species ◽  
Bone Surface ◽  
Skull Morphology

Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen.

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