About Noggin:
Noggin (also known as NOG) is a protein involved with the development of many different body tissues such as nerve tissues, bones and muscles. In human development, noggin is encoded by the NOG gene. The amino acid sequence of noggin is high homologous to that of rats, mice and Xenopus (an aquatic-frog genus).
Noggin’s name is slang for the word “head”. This nickname was coined due to its ability to produce embryos with large heads when exposed at high concentrations.
Discovery
Noggin was discovered by Richard M. Harland and William C. Smith at the University of California, Berkeley. Noggin was first isolated from Xenopus, an aquatic-frog genus. This discovery was based on the organism’s ability to restore normal dorsal-ventral body axis in embryos that had been ventralized artificially from UV treatment.
Mechanism
The secreted polypeptide noggin is encoded by the NOG gene. It binds and inactivates members of the transforming growth factor-beta (TGF-beta) superfamily signalling proteins, such as bone morphogenetic protein-4 (BMP4). By diffusing through extracellular matrices more efficiently than other members of the TGF-beta superfamily, noggin is believed to have a principal role in creating morphogenic gradients. Noggin also appears to have pleiotropic effects in both early development and later stages.
Function
Noggin is a signalling molecule that plays a critical role in promoting somite patterning in the developing embryo. It’s released from the notochord and regulates bone morphogenic protein (BMP4) during development. The absence of this protein causes the patterning of the neural tube and somites from the neural plate in the developing embryo. It also causes the head and other dorsal structures to form.
Noggin function is required for correct skeletal, somite and nervous system development. In experiments on mice, noggin has shown to also play a part in learning, cognition, bone development and neural tube fusion. Heterozygous missense mutations in the noggin gene can also cause deformities like joint fusions and syndromes such as multiple synostosis syndrome and proximal symphalangism.
Significance
Noggin protein plays a vital role in germ layer-specific derivation of specialized cells. The formation of the notochord, hair follicles, neural tissues and eye structures arise from the ectoderm germ layer. Noggin activity in the mesoderm paves the way for the formation of cartilage, bone and muscle growth. In the endoderm, noggin is involved in lung development.
During the early stages of craniofacial development, the presence of noggin heavily influences the formation and growth of the palate, mandible and skull. This happens through its interaction with neural crest cells. Mice that are shown to have an outgrowth of the mandible and a cleft palate lack the NOG gene. The absence of noggin also causes conductive hearing loss due to an uncontrolled outgrowth of the cochlear duct and coiling.