Noggin protein

: Also known as NOG

The NOG gene provides instructions for making a protein called noggin. This protein is involved in the development of many body tissues, including nerve tissue, muscles, and bones. Noggin's role in bone development makes it important for proper joint formation.

Noggin interacts with members of a group of proteins called bone morphogenetic proteins (BMPs). These proteins help control the development of bone and other tissues. In order to begin these developmental processes, BMPs attach (bind) to other proteins called receptors, and this binding stimulates specific cellular processes. The noggin protein regulates the activity of certain BMPs by attaching to them and blocking them from binding to the receptor, which leads to a decrease in BMP signaling.

Tarsal-carpal coalition syndrome: caused by mutations in the NOG gene

Characterized by:  fusion of the individual bones in the wrists (the carpal bones) and in the ankles (the tarsal bones) as well as fusion at the joints between the bones that make up each finger and toe (symphalangism). Symphalangism makes the fingers and toes stiff and difficult to bend.

Bone morphogenetic proteins (BMPs)

A group of growth factors also known as cytokines and as metabologens. Also, a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. They have ability to induce the formation of bone and cartilage.

They have an important role during embryonic development on the embryonic patterning and early skeletal formation. As such, disruption of BMP signaling can affect the body plan of the developing embryo. BMp4 and its inhibitors noggin and chordin help regulate polarity of the embryo. Specifically BMP-4 and its inhibitors play a major role in neurulation and the development of the neural plate. BMP-4 signals ectoderm cells to develop into skin cells, but the secretion of inhibitors by the underlying mesoderm blocks the action of BMP-4 to allow the ectoderm to continue on its normal course of neural cell development.

Chimeras

Chimeras are animals composed of cells that originate from two (or more) different species. In the research lab, chimeras are created by introducing cells from one species into the developing embryo or fetus of another. (The name chimera comes from Greek mythology and describes a creature with the head of a lion, the body of a goat, and the tail of a serpent).

The first chimeras helped scientists understand questions about developmental biology. A sheep-goat chimera, created in 1984, had the head of a goat and the woolly coat of a sheep.

Now, researchers are developing human-animal chimeras to study disease processes, test new drugs, and develop organs for future transplant patients. The chimeras are produced by introducing human stem cells into developing animal embryos.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Spemann.html

http://ghr.nlm.nih.gov/gene/NOG

Homeobox protein Siamois

Gene: Siamois

Organism: xenopuus laevis  (African clawed frog)

Essential for Wnt/beta-catenin-mediated formation of the Spemann organizer and for induction of the organizer precursor, the Nieuwkoop center. Acts as a transcriptional activator, cooperating with TGFbeta signals to induce a program of organizer-specific gene expression and to generate an organizer with both head- and trunk-inducing activity. Activates the head organizer gene cer1 by acting synergistically with otx2 and mix-A/mix.1 through the 5'-TAATCT-3' element of the cer1 promoter. Also binds as a complex with lhx1/lim1 and mix-A/mix.1 to the 3x 5'-TAAT-3' element of the cer1 promoter. Required for subsequent dorsoventral axis formation in the embryo, dorsalizing ventral mesoderm and cooperating with t/bra to induce dorsal mesoderm. Also involved in neural induction, inducing the cement gland and neural tissue in overlying ectoderm. Later in development, has the second function of indirectly repressing ventral genes, probably by activating the expression of a transcriptional repressor.

Homeobox protein goosecoid

Gene: GSC

Organism: Homo sapiens (Human)

Regulates chordin (CHRD). May play a role in spatial programing within discrete embryonic fields or lineage compartments during organogenesis. In concert with NKX3-2, plays a role in defining the structural components of the middle ear; required for the development of the entire tympanic ring by similarity. Probably involved in the regulatory networks that define neural crest cell fate specification and determine mesoderm cell lineages in mammals.

A mutation in the GSC gene causes short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS). Mutations in the Gsc gene can lead to specific phenotypes resulting from the second expression of the Gsc gene during organogenesis. Mice knock-out models of the gene express defects in the tongue, nasal cavity, nasal pits, inner ear, and external auditory meatus.

Chordin-like protein 1

Gene: CHRDL1

Organism: Homo sapiens (Human)

Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors. Alters the fate commitment of neural stem cells from gliogenesis to neurogenesis. Contributes to neuronal differentiation of neural stem cells in the brain by preventing the adoption of a glial fate. May play a crucial role in dorsoventral axis formation. May play a role in embryonic bone formation by similarity. May also play an important role in regulating retinal angiogenesis through modulation of BMP4 actions in endothelial cells. Plays a role during anterior segment eye development.

https://www.wikigenes.org/e/gene/e/12667.html

http://www.sciencedirect.com/science/article/pii/S0960982298000098

Thanatophoric dysplasia

Thanatophoric Dysplasia(TD)

: is the most common form of skeletal dysplasia( severe skeletal disorder) , lethal in the neonatal period .

Characterized by:  extremely short limbs, folds of extra skin on the arms and legs, a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes.

Type I thanatophoric dysplasia: presence of curved thigh bones and flattened bones of the spine (platyspondyly). 

Type II thanatophoric dysplasia:  straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.

cause: 

Mutations in the FGFR3 gene (the short-arm of chromosome 4)

 FGFR3 gene: encoded Fibroblast growth factor receptor 3 protein in human. It is involved in the development and maintenance of bone and brain tissue. Mutations in this gene cause the FGFR3 protein to be overly active, which leads to the severe disturbances in bone growth that are characteristic of thanatophoric dysplasia.

FGFR3 protein is part of the tyrosine kinase receptor family. FGFR3 is a negative regulator of bone growth.

Thanatophoric dysplasia initiate by sending negative signals to the cartilage cells .These signals occur when ligand binding within the chondrocytes induces receptor homodimerization and heterodimerization. As aresult, activation of tyrosine kinase function potentiates many effects on cell growth and differentiation.

http://emedicine.medscape.com/article/949591-overview#a0104

http://ghr.nlm.nih.gov/condition/thanatophoric-dysplasia