scholarly journals Tbx1 and Foxi3 genetically interact in the third pharyngeal pouch endoderm required for thymus and parathyroid development

2018 ◽  
Author(s):  
Erica Hasten ◽  
Bernice E Morrow
Keyword(s):  
Adherens Junctions ◽  
Mammalian Species ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Pharyngeal Pouch ◽  
22Q11.2 Deletion ◽  
The Third ◽  
Transcription Factor Genes ◽  
Pharyngeal Apparatus ◽  
Third Pharyngeal Pouch

SummaryThe mechanisms required for segmentation of the pharyngeal apparatus to individual arches are not precisely delineated in mammalian species. Here, using conditional mutagenesis, we found that two transcription factor genes, Tbx1, the gene for 22q11.2 deletion syndrome and Foxi3, genetically interact in the third pharyngeal pouch endoderm for thymus and parathyroid gland development. We found that Tbx1 is autonomously required for the endoderm to form a temporary multilayered epithelium while invaginating. E-cadherin for adherens junctions remains expressed and cells in the apical boundary express ZO-1. Foxi3 is required autonomously to modulate proliferation and promote later restoration of the endoderm to a monolayer once the epithelia meet after invagination. Completion of this process cooccurs with expression of Alcam needed to stabilize adherens junctions and extracellular, Fibronectin. These processes are required in the third pharyngeal pouch to form the thymus and parathyroid glands, disrupted in 22q11.2 deletion syndrome patients.

scholarly journals Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in the murine cardiopharyngeal mesoderm

2020 ◽  
Author(s):  
Hiroko Nomaru ◽  
Yang Liu ◽  
Christopher De Bono ◽  
Dario Righelli ◽  
Andrea Cirino ◽  
...  
Keyword(s):  
Single Cell ◽  
22Q11.2 Deletion Syndrome ◽  
Chromatin Accessibility ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
T Box ◽  
Single Cell Rna Sequencing ◽  
Pharyngeal Apparatus ◽  
The Face ◽  
Continuous Source

AbstractThe poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm (CPM) within the pharyngeal apparatus. The formation of the cardiac outflow tract and branchiomeric muscles are disrupted in patients with 22q11.2 deletion syndrome (22q11.2DS), due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we identified a multilineage primed population (MLP) within the CPM, marked by the Tbx1 lineage, which has bipotent properties to form cardiac and skeletal muscle cells. The MLPs are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of progenitors that undergo TBX1-dependent progression towards maturation. Tbx1 also regulates the balance between MLP maintenance and maturation while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance by direct regulation of MLP enriched genes and downstream pathways, partly through altering chromatin accessibility. Our study thus uncovers a new cell population and reveals novel mechanisms by which Tbx1 directs the development of the pharyngeal apparatus, which is profoundly altered in 22q11.2DS.

scholarly journals Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hiroko Nomaru ◽  
Yang Liu ◽  
Christopher De Bono ◽  
Dario Righelli ◽  
Andrea Cirino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
22Q11.2 Deletion Syndrome ◽  
Chromatin Accessibility ◽  
Deletion Syndrome ◽  
Congenital Defects ◽  
22Q11.2 Deletion ◽  
T Box ◽  
Pharyngeal Apparatus ◽  
The Face

AbstractThe poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm within the pharyngeal apparatus. They are disrupted in patients with 22q11.2 deletion syndrome, due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we now identify a multilineage primed population within the cardiopharyngeal mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells. The multilineage primed cells are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of cardiopharyngeal mesoderm progenitors. Tbx1 regulates the maturation of multilineage primed progenitor cells to cardiopharyngeal mesoderm derivatives while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance of gene expression by direct and indirect regulation of enriched genes in multilineage primed progenitors and downstream pathways, partly through altering chromatin accessibility, the perturbation of which can lead to congenital defects in individuals with 22q11.2 deletion syndrome.

Surgical Management of Patients With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (5) ◽  
pp. 857-869
Author(s):  
Oksana A. Jackson ◽  
Alison E. Kaye
Keyword(s):  
Surgical Management ◽  
Preoperative Evaluation ◽  
Preoperative Assessment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Surgical Decision ◽  
Obstructive Sleep ◽  
Spine Abnormalities ◽  
Speech Assessment

Purpose The purpose of this tutorial was to describe the surgical management of palate-related abnormalities associated with 22q11.2 deletion syndrome. Craniofacial differences in 22q11.2 deletion syndrome may include overt or occult clefting of the palate and/or lip along with oropharyngeal variances that may lead to velopharyngeal dysfunction. This chapter will describe these circumstances, including incidence, diagnosis, and indications for surgical intervention. Speech assessment and imaging of the velopharyngeal system will be discussed as it relates to preoperative evaluation and surgical decision making. Important for patients with 22q11.2 deletion syndrome is appropriate preoperative screening to assess for internal carotid artery positioning, cervical spine abnormalities, and obstructive sleep apnea. Timing of surgery as well as different techniques, common complications, and outcomes will also be discussed. Conclusion Management of velopharyngeal dysfunction in patients with 22q11.2 deletion syndrome is challenging and requires thoughtful preoperative assessment and planning as well as a careful surgical technique.

Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

2019 ◽  
Vol 4 (4) ◽  
pp. 633-640 ◽  
Author(s):  
Canice E. Crerand ◽  
Ari N. Rabkin
Keyword(s):  
Cognitive Abilities ◽  
Psychotic Disorders ◽  
Developmental Stages ◽  
Early Adulthood ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Psychosocial Risks ◽  
Empirically Supported ◽  
Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

Conotruncal heart defects and aortic arch anomalies in fetuses with 22q11.2 deletion syndrome

2020 ◽  
Author(s):  
I.V. Novikova, O.M. Khurs, T.V. Demidovich et all
Keyword(s):  
Aortic Arch ◽  
Heart Defects ◽  
22Q11.2 Deletion Syndrome ◽  
Ventricular Outflow Tract ◽  
Double Outlet Right Ventricle ◽  
Interrupted Aortic Arch ◽  
Left Ventricular ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Aortic Arch Anomalies

16 second trimester fetuses with 22q11.2 deletion syndrome have been examined at anatomic-pathological investigation. Main cardiovascular diseases were ascending aorta hypoplasia with aortic valve stenosis (n = 6; 37.5%), truncus arteriosus (n = 5; 31.25%), tetralogy of Fallot (n = 3; 18.75%) and double-outlet right ventricle (n = 1; 6.25%). Ventricular septal defect was present in 16 cases. Associated aortic arch anomalies included interrupted aortic arch (n = 9; 56.25%), right aortic arch (n = 6; 37.5%), retroesophageal ring (n = 1; 6.25%) and aberrant right subclavian arteria (n = 5; 31.25%). 5 fetuses had left ventricular outflow tract obstructive lesions with interrupted aortic arch of type B combined with aberrant right subclavian arteria.

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