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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, wh ...
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Ectoderm
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the outer layer of germ cells. The word ectoderm comes from the Greek ''ektos'' meaning "outside", and ''derma'' meaning "skin".Gilbert, Scott F. Developmental Biology. 9th ed. Sunderland, MA: Sinauer Associates, 2010: 333-370. Print. Generally speaking, the ectoderm differentiates to form epithelial and neural tissues ( spinal cord, peripheral nerves and brain). This includes the skin, linings of the mouth, anus, nostrils, sweat glands, hair and nails, and tooth enamel. Other types of epithelium are derived from the endoderm. In vertebrate embryos, the ectoderm can be divided into two parts: the dorsal surface ectoderm also known as the external ectoderm, and the neural plate, which invaginates to form the neural tube and neural c ...
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Hamburger–Hamilton Stages
In developmental biology, the Hamburger–Hamilton stages (HH) are a series of 46 chronological stages in chick development, starting from laying of the egg and ending with a newly hatched chick. It is named for its creators, Viktor Hamburger and Howard L. Hamilton. Chicken embryos are a useful model organism in experimental embryology for a number of reasons. Their domestication as poultry makes them more readily available than other vertebrates (such as mice), and being oviparous, the embryos are easily accessible. However, the rate of development can be affected by a range of factors; including the specific breed, the temperature of incubation, the delay between laying and incubation, and the time of year, raising the need to create a standardised system based on morphology rather than chronological age. There had been a previous attempt to create a morphological system for staging chick development by the German embryologists Keibel and Abraham in 1900, but this system lac ...
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Bone Morphogenetic Proteins
Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signalling in pathological processes. Cancerous disease often involves misregulation of the BMP signalling system. Absence of BMP signalling is, for instance, an important factor in the progression of colon cancer, and conversely, overactivation of BMP signalling following reflux-induced esophagitis provokes Barrett's esophagus and is thus instrumental in the development of esophageal adenocarcinoma. Recombinant human BMPs (rhBMPs) are used in orthopedic applications such as spinal fusions, nonunions, and oral surgery. rhBMP-2 and rhBMP-7 ...
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Hox Genes
Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment (for example, legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves. Studies on Hox genes in ciliated larvae have shown they are only expressed in future adult tissues. In larvae with gradual metamorphosis the Hox genes are activated in tissues of the larval body, generally in the trunk region, that will be maintained through metamorphosis. In larvae with complete metamorphosis the Hox genes are mainly expres ...
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Fibroblast Growth Factor
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling. Families In humans, 23 members of the FGF family have been identified, all of which are ''structurally'' related signaling molecules: * Members FGF1 through FGF10 all bind fibroblast growth factor receptors (FGFRs). FGF1 is also known as ''acidic fibroblast growth factor'', and FGF2 is also kno ...
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Bone Morphogenic Protein
Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signalling in pathological processes. Cancerous disease often involves misregulation of the BMP signalling system. Absence of BMP signalling is, for instance, an important factor in the progression of colon cancer, and conversely, overactivation of BMP signalling following reflux-induced esophagitis provokes Barrett's esophagus and is thus instrumental in the development of esophageal adenocarcinoma. Recombinant human BMPs (rhBMPs) are used in orthopedic applications such as spinal fusions, nonunions, and oral surgery. rhBMP-2 and rhBMP-7 are ...
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Gremlin (protein)
Gremlin is an inhibitor in the TGF beta signaling pathway. It primarily inhibits bone morphogenesis and is implicated in disorders of increased bone formation and several cancers. Structure Gremlin1, previously known as Drm, is a highly conserved 20.7-kDa, 184 amino acid glycoprotein part of the DAN family and is a cysteine knot-secreted protein. Gremlin1 was first identified in differential screening as a transcriptional down-regulated gene in v-mos-transformed rat embryonic fibroblasts. Function Gremlin1 (Grem1) is known for its antagonistic interaction with bone morphogenetic proteins (BMPs) in the TGF beta signaling pathway. Grem1 inhibits predominantly BMP2 and BMP4 in limb buds and functions as part of a self-regulatory feedback signaling system, which is essential for normal limb bud development and digit formation. Inhibition of BMPs by Grem1 in limb buds allows the transcriptional up-regulation of the fibroblast growth factors (FGFs) 4 and 8 and sonic hedgehog (S ...
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Sonic Hedgehog
Sonic hedgehog protein (SHH) is encoded for by the ''SHH'' gene. The protein is named after the character ''Sonic the Hedgehog (character), Sonic the Hedgehog''. This signaling molecule is key in regulating embryonic morphogenesis in all animals. SHH controls organogenesis and the organization of the central nervous system, limbs, digits and many other parts of the body. Sonic hedgehog is a morphogen that patterns the developing embryo using a concentration gradient characterized by the French flag model. This model has a non-uniform distribution of SHH molecules which governs different cell fates according to concentration. Mutations in this gene can cause holoprosencephaly, a failure of splitting in the cerebral hemispheres, as demonstrated in an experiment using SHH knock-out mice in which the forebrain midline failed to develop and instead only a single fused telencephalic vesicle resulted. Sonic hedgehog still plays a role in differentiation, proliferation, and maintenance ...
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WNT3A
Protein Wnt-3a is a protein that in humans is encoded by the ''WNT3A'' gene. The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have are critical in tissue homeostasis, embryonic development, and disease. Signaling and Related Genes WNT3A is highly related to the WNT3 gene in sequence and protein function. WNT3A and WNT3 signal similarly through primarily the beta-catenin/Tcf pathway. WNT3A is located in the genome beside the WNT9A gene across many vertebrates. Similarly, the WNT3 gene occurs in the genome beside the WNT9B gene. WNT9A and WNT9B signal through the beta-catenin/Tcf pathway but do not play related roles as WNT3A and WNT3 in the same cellular processes. Role in Disease WNT3A is not linked to particular genetic disorder in humans. Mice that have a genetic mutation in the WNT3A die during early embryogenesis and fail to correctly form axial tissues. Wnt-3a promotes the beta-catenin/Tcf pathwa ...
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WNT2B
Protein Wnt-2b (formerly Wnt13) is a protein that in humans is encoded by the ''WNT2B'' gene. This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as human carcinogenesis. This gene produces two alternative transcript variant Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be in ...s. References Further reading

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