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Tbx4
T-box refers to a group of transcription factors involved in embryonic limb and heart development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein that is both necessary and sufficient for sequence-specific DNA binding. All members of the T-box gene family bind to the "T-box", a DNA consensus sequence of TCACACCT. Members T-boxes are especially important to the development of embryos, found in zebrafish oocyte by Bruce et al 2003 and '' Xenopus laevis'' oocyte by Xanthos et al 2001. They are also expressed in later stages, including adult mouse and rabbit studied by Szabo et al 2000. Mutations in the first one found caused short tails in mice, and thus the protein encoded was named brachyury, Greek for "short-tail". In mice this gene is named ''Tbxt'', and in humans it is named '' TBXT''. Brachyury has been found in all bilaterian animals that have been screened, and is also present in the cnidaria. T ...
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Limb Bud
The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In human embryonic development, the development of the human embryo the upper limb bud appears in the third week and the lower limb bud appears four days later. The limb bud consists of undifferentiated mesoderm cells that are sheathed in ectoderm. As a result of cell signaling interactions between the ectoderm and underlying mesoderm cells, formation of the developing limb bud occurs as mesenchyme, mesenchymal cells from the lateral plate mesoderm and somites begin to proliferate to the point where they create a bulge under the ectodermal cells above. The mesoderm cells in the limb bud that come from the lateral plate mesoderm will eventually differentiate into the developing limb's connective tissues, such as cartilage, bone, and tendon. Moreover, the mesoderm cells that ...
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Limb Development
Limb development in vertebrates is an area of active research in both developmental and evolutionary biology, with much of the latter work focused on the transition from fin to limb. Limb formation begins in the morphogenetic limb field, as mesenchymal cells from the lateral plate mesoderm proliferate to the point that they cause the ectoderm above to bulge out, forming a limb bud. Fibroblast growth factor (FGF) induces the formation of an organizer at the end of the limb bud, called the apical ectodermal ridge (AER), which guides further development and controls cell death. Programmed cell death is necessary to eliminate webbing between digits. The limb field is a region specified by expression of certain Hox genes, a subset of homeotic genes, and T-box transcription factors – Tbx5 for forelimb or wing development, and Tbx4 for leg or hindlimb development. Establishment of the forelimb field (but not hindlimb field) requires retinoic acid signaling in the developing trun ...
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TBX5 (gene)
T-box transcription factor TBX5, (T-box protein 5) is a protein that in humans is encoded by the ''TBX5'' gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt–Oram syndrome, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. ''TBX5'' is located on the long arm of chromosome 12. ''TBX5'' produces a protein called T-box protein 5 that acts as a transcription factor. ''TBX5'' is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering fibroblast growth factor, FGF10. Function ''TBX5'' is a transcription factor that codes for the protein call ...
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TBX5
T-box transcription factor TBX5, (T-box protein 5) is a protein that in humans is encoded by the ''TBX5'' gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. ''TBX5'' is located on the long arm of chromosome 12. ''TBX5'' produces a protein called T-box protein 5 that acts as a transcription factor. ''TBX5'' is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering fibroblast growth factor, FGF10. Function ''TBX5'' is a transcription factor that codes for the protein called T-box 5. The tra ...
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TBX4
T-box refers to a group of transcription factors involved in embryonic limb and heart development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein that is both necessary and sufficient for sequence-specific DNA binding. All members of the T-box gene family bind to the "T-box", a DNA consensus sequence of TCACACCT. Members T-boxes are especially important to the development of embryos, found in zebrafish oocyte by Bruce et al 2003 and '' Xenopus laevis'' oocyte by Xanthos et al 2001. They are also expressed in later stages, including adult mouse and rabbit studied by Szabo et al 2000. Mutations in the first one found caused short tails in mice, and thus the protein encoded was named brachyury, Greek for "short-tail". In mice this gene is named ''Tbxt'', and in humans it is named '' TBXT''. Brachyury has been found in all bilaterian animals that have been screened, and is also present in the cnidaria. T ...
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TBX3
T-box transcription factor TBX3 is a protein that in humans is encoded by the ''TBX3'' gene. T-box 3 (TBX3) is a member of the T-box gene family of transcription factors which all share a highly conserved DNA binding domain known as the T-box. The T-box gene family consists of 17 members in mouse and humans that are grouped into five subfamilies, namely Brachyury (T), T-brain (Tbr1), TBX1, TBX2, and TBX6. Tbx3 is a member of the Tbx2 subfamily which includes Tbx2, Tbx4 and Tbx5. The human TBX3 gene maps to chromosome 12 at position 12q23-24.1 and consists of 7 exons which encodes a 723 amino acid protein (ENSEMBL assembly release GRCh38.p12). Transcript splicing Alternative processing and splicing results in at least 4 distinct TBX3 isoforms with TBX3 and TBX3+2a being the predominant isoforms. TBX3+2a results from alternative splicing of the second intron which leads to the addition of the +2a exon and consequently this isoform has an additional 20 amino acids within the T-b ...
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Apical Ectodermal Ridge
The apical ectodermal ridge (AER) is a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a limb. After the limb bud induces AER formation, the AER and limb mesenchyme—including the zone of polarizing activity (ZPA)—continue to communicate with each other to direct further limb development. The position of the limb bud, and hence the AER, is specified by the expression boundaries of Hox genes in the embryonic trunk. At these positions, the induction of cell outgrowth is thought to be mediated by a positive feedback loop of fibroblast growth factors (FGFs) between the intermediate mesoderm, the lateral plate mesoderm and the surface ectoderm. FGF8 in the intermediate mesoderm signals to the lateral mesoderm, restricting the expression of FGF10 through intermediate Wnt signals. Then, FGF10 in the lateral plate mesoderm signals to the surface ectoderm to create the AER, whi ...
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X-ray Crystallography
X-ray crystallography is the experimental science of determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to Diffraction, diffract in specific directions. By measuring the angles and intensities of the X-ray diffraction, a crystallography, crystallographer can produce a three-dimensional picture of the density of electrons within the crystal and the positions of the atoms, as well as their chemical bonds, crystallographic disorder, and other information. X-ray crystallography has been fundamental in the development of many scientific fields. In its first decades of use, this method determined the size of atoms, the lengths and types of chemical bonds, and the atomic-scale differences between various materials, especially minerals and alloys. The method has also revealed the structure and function of many biological molecules, including vitamins, drugs, proteins and nucleic acids such as DNA. X-ray crystall ...
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Ventricle (heart)
A ventricle is one of two large chambers located toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium, an adjacent chamber in the upper heart that is smaller than a ventricle. Interventricular means between the ventricles (for example the interventricular septum), while intraventricular means within one ventricle (for example an intraventricular block). In a four-chambered heart, such as that in humans, there are two ventricles that operate in a double circulatory system: the right ventricle pumps blood into the pulmonary circulation to the lungs, and the left ventricle pumps blood into the systemic circulation through the aorta. Structure Ventricles have thicker walls than atria and generate higher blood pressures. The physiological load on the ventricles requiring pumping of blood throughout the body and lungs is much greater than the pressure generated by ...
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Ventricular Septal Defect
A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. It's a common heart problem present at birth ( congenital heart defect). The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one common ventricle. The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes. The membranous portion, which is close to the atrioventricular node, is most commonly affected in adults and older children in the United States. It is also the type that will most commonly require surgical intervention, comprising over 80% of cases. Membranous ventricular septal defects are more common than muscular ventricular septal defects, and are the most common congenital cardiac anomaly. Signs and symptoms Ventricular septal defect is usually symptomless at birth. It usually manifests a fe ...
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Carpal Bones
The carpal bones are the eight small bones that make up the wrist (carpus) that connects the hand to the forearm. The terms "carpus" and "carpal" are derived from the Latin wikt:carpus#Latin, carpus and the Greek language, Greek wikt:καρπός#Ancient Greek, καρπός (karpós), meaning "wrist". In human anatomy, the main role of the carpal bones is to joint, articulate with the radius (bone), radial and ulnar heads to form a highly mobile condyloid joint (i.e. wrist joint),Kingston 2000, pp 126-127 to provide attachments for thenar and hypothenar muscles, and to form part of the rigid carpal tunnel which allows the median nerve and tendons of the anterior compartment of the forearm, anterior forearm muscles to be transmitted to the hand and fingers. In tetrapods, the carpus is the sole cluster of bones in the wrist between the radius (bone), radius and ulna and the metacarpus. The bones of the carpus do not belong to individual fingers (or toes in quadrupeds), whereas those ...
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Holt–Oram Syndrome
Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and often causes heart problems. The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block. It affects approximately 1 in 100,000 people. Presentation All people with Holt-Oram syndrome have at least one abnormal wrist bone, which can often only be detected by X-ray. Other bone abnormalities are associated with the syndrome. These vary widely in severity, and include a missing thumb, a thumb that looks like a finger, upper arm bones of unequal length or underdeveloped, partial or complete absence of bones in the forearm, and abnormalities in the collar bone or shoulder blade. Bone abnormalities may affect only one side of the body or both sides; if both sides ar ...
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