scholarly journals PRDM proteins control Wnt/β-catenin activity to regulate craniofacial chondrocyte differentiation

2021 ◽  
Author(s):  
Lomeli Carpio Shull ◽  
Hyun Min Kim ◽  
Ezra Lencer ◽  
James C Costello ◽  
Kenneth Jones ◽  
...  
Keyword(s):  
Birth Defects ◽  
Transcriptional Activity ◽  
Global Gene Expression ◽  
Chromatin Accessibility ◽  
Cartilage Defects ◽  
Chondrocyte Differentiation ◽  
Maturation Process ◽  
Craniofacial Skeleton ◽  
Congenital Birth Defects ◽  
Cartilage Differentiation

Cranial neural crest (NCC)-derived chondrocyte precursors undergo a dynamic differentiation and maturation process to establish a scaffold for subsequent bone formation, alterations in which contribute to congenital birth defects. Here, we demonstrate that transcription factor and histone methyltransferase proteins Prdm3 and Prdm16 control the differentiation switch of cranial NCCs to craniofacial cartilage. Loss of either results in hypoplastic and unorganized chondrocytes due to impaired cellular orientation and polarity. We show that PRDMs regulate cartilage differentiation by controlling the timing of Wnt/β-catenin activity in strikingly different ways: Prdm3 represses while Prdm16 activates global gene expression, though both by regulating Wnt enhanceosome activity and chromatin accessibility. Finally, we show that manipulating Wnt/β-catenin signaling pharmacologically or generating prdm3-/-;prdm16-/- double mutants rescues craniofacial cartilage defects. Our findings reveal upstream regulatory roles for Prdm3 and Prdm16 in cranial NCCs to control Wnt/β-catenin transcriptional activity during chondrocyte differentiation to ensure proper development of the craniofacial skeleton.

TBX1 Regulates Chondrocyte Maturation in the Spheno-occipital Synchondrosis

2020 ◽  
Vol 99 (10) ◽  
pp. 1182-1191 ◽  
Author(s):  
N. Funato ◽  
D. Srivastava ◽  
S. Shibata ◽  
H. Yanagisawa
Keyword(s):  
Digeorge Syndrome ◽  
Endochondral Ossification ◽  
Transcriptional Activity ◽  
Ectopic Expression ◽  
Chondrocyte Differentiation ◽  
Craniofacial Skeleton ◽  
Chondrocyte Maturation ◽  
Expression Of Genes ◽  
Growth Center ◽  
Deficient Mice

The synchondrosis in the cranial base is an important growth center for the craniofacial region. Abnormalities in the synchondroses affect the development of adjacent regions, including the craniofacial skeleton. Here, we report that the transcription factor TBX1, the candidate gene for DiGeorge syndrome, is expressed in mesoderm-derived chondrocytes and plays an essential and specific role in spheno-occipital synchondrosis development by inhibiting the expression of genes involved in chondrocyte hypertrophy and osteogenesis. In Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth. TBX1 interacts with RUNX2, a master molecule of osteoblastogenesis and a regulator of chondrocyte maturation, and suppresses its transcriptional activity. Indeed, deleting Tbx1 triggers accelerated mineralization due to accelerated chondrocyte differentiation, which is associated with ectopic expression of downstream targets of RUNX2 in the spheno-occipital synchondrosis. These findings reveal that TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development. Thus, the tight regulation of endochondral ossification by TBX1 is crucial for the normal progression of chondrocyte differentiation in the spheno-occipital synchondrosis.

scholarly journals The Skull’s Girder: A Brief Review of the Cranial Base

2021 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Shankar Rengasamy Venugopalan ◽  
Eric Van Otterloo
Keyword(s):  
Birth Defects ◽  
Vertebral Column ◽  
Endochondral Ossification ◽  
Cranial Base ◽  
Facial Skeleton ◽  
The Core ◽  
Skull Vault ◽  
Congenital Birth Defects ◽  
Intimate Association ◽  
The Brain

The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and seamlessly integrates with the facial skeleton at its rostral end. Unique from the majority of the cranial skeleton, the cranial base develops from a cartilage intermediate—the chondrocranium—through the process of endochondral ossification. Owing to the intimate association of the cranial base with nearly all aspects of the head, congenital birth defects impacting these structures often coincide with anomalies of the cranial base. Despite this critical importance, studies investigating the genetic control of cranial base development and associated disorders lags in comparison to other craniofacial structures. Here, we highlight and review developmental and genetic aspects of the cranial base, including its transition from cartilage to bone, dual embryological origins, and vignettes of transcription factors controlling its formation.

scholarly journals Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fabien Aubry ◽  
Sofie Jacobs ◽  
Maïlis Darmuzey ◽  
Sebastian Lequime ◽  
Leen Delang ◽  
...  
Keyword(s):  
Birth Defects ◽  
Zika Virus ◽  
Public Health Surveillance ◽  
Fetal Loss ◽  
Surveillance Systems ◽  
Apparent Paradox ◽  
Congenital Birth Defects ◽  
Fetal Mice ◽  
Puzzling Aspect ◽  
Low Passage

AbstractThe global emergence of Zika virus (ZIKV) revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compare seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We find that recent African ZIKV strains display higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice than their Asian counterparts. We emphasize the high epidemic potential of African ZIKV strains and suggest that they could more easily go unnoticed by public health surveillance systems than Asian strains due to their propensity to cause fetal loss rather than birth defects.

scholarly journals Clinically Visible Congenital Birth Defects, Case of the Kenya Health District in the Democratic Republic of the Congo

OALib ◽  
2019 ◽  
Vol 06 (05) ◽  
pp. 1-7
Author(s):  
Nama Mwengu Cecile ◽  
Mizelo waKumwimba ◽  
Ngoy Shindano Romain ◽  
Iungamakonga Dressen ◽  
Lunkutu kitambala Hugues ◽  
...  
Keyword(s):  
Birth Defects ◽  
Democratic Republic ◽  
Health District ◽  
Congenital Birth Defects ◽  
Republic Of The Congo

scholarly journals TRACTION CONCEPT «REHABILITATION» IN THE FRENCH MEDICINE SYSTEM

World Science ◽  
2019 ◽  
Vol 2 (5(45)) ◽  
pp. 4-6
Author(s):  
M. Danylevych ◽  
R. Koval ◽  
B. Ivanytska ◽  
Y. Kazimova
Keyword(s):  
Twentieth Century ◽  
Everyday Life ◽  
Birth Defects ◽  
21St Century ◽  
State Power ◽  
Physical Culture ◽  
Social Phenomenon ◽  
Persons With Disabilities ◽  
Congenital Birth Defects ◽  
Tools And Methods

Given the increase on the planet of the number of people with congenital birth defects, technocratization of society, an increase in the number of persons with disabilities was expected at the beginning of the 21st century to one billion consequently, disability is a worldwide social phenomenon, which should be the focus of every country, its bodies of state power and administration, scientists and physicians, psychologists and educators, specialists in physical culture and sports. So, we see that under the concept «réadaptation» (f) in France, a set of tools and methods used by the relevant specialists to rehabilitate persons with disabilities, as well as simply patients, in order to return them to the maximum possible conditions of everyday life. The twentieth century in France is characterized by the creation of a number of organizations whose activities are aimed at working with such people.

scholarly journals Risk of congenital birth defects during COVID-19 pandemic: Draw attention to the physicians and policymakers

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Md Sakirul Islam Khan ◽  
Hiroaki Nabeka ◽  
Sheikh Mohammad Fazle Akbar ◽  
Mamun Al Mahtab ◽  
Tetsuya Shimokawa ◽  
...  
Keyword(s):  
Birth Defects ◽  
Congenital Birth Defects

scholarly journals Developing Practical Therapeutic Strategies that Target Protein SUMOylation

2019 ◽  
Vol 20 (9) ◽  
pp. 960-969 ◽  
Author(s):  
Olivia F. Cox ◽  
Paul W. Huber
Keyword(s):  
Birth Defects ◽  
Inflammatory Disease ◽  
Intracellular Localization ◽  
Specific Protein ◽  
Therapeutic Strategies ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Protein Activity ◽  
Multiple Components ◽  
Congenital Birth Defects

Post-translational modification by small ubiquitin-like modifier (SUMO) has emerged as a global mechanism for the control and integration of a wide variety of biological processes through the regulation of protein activity, stability and intracellular localization. As SUMOylation is examined in greater detail, it has become clear that the process is at the root of several pathologies including heart, endocrine, and inflammatory disease, and various types of cancer. Moreover, it is certain that perturbation of this process, either globally or of a specific protein, accounts for many instances of congenital birth defects. In order to be successful, practical strategies to ameliorate conditions due to disruptions in this post-translational modification will need to consider the multiple components of the SUMOylation machinery and the extraordinary number of proteins that undergo this modification.

scholarly journals Modeling craniofacial and skeletal congenital birth defects to advance therapies

2016 ◽  
Vol 25 (R2) ◽  
pp. R86-R93 ◽  
Author(s):  
Cynthia L. Neben ◽  
Ryan R. Roberts ◽  
Katrina M. Dipple ◽  
Amy E. Merrill ◽  
Ophir D. Klein
Keyword(s):  
Birth Defects ◽  
Congenital Birth Defects
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