Multiple Roles of Noggin, a BMP Antagonist, in Development of Craniofacial Skeletal Elements and Neural Tube

Abstract

Proper morphogenesis is essential for both form and function of mammalian craniofacial and neural tube development. Craniofacial deformities and neural tube defects are highly prevalent human birth defects. Although studies concerning craniofacial and neural tube development have revealed important genetic and/or environmental factors, understanding the mechanisms underlying proper development and the defects remain incomplete. Among many genes that were cloned as the gastrula organizer genes in 1990s, Nog, a secreted BMP antagonist, is expressed in the relevant domains during craniofacial and neural tube development. Previous studies show that Nog null embryos exhibit fully penetrant spina bifida (open spine) and to the lesser extent exencephaly (open brain). Moreover, Nog null mice display deformities in skeletal structures including defects in craniofacial skeleton. As such, Nog is essential for proper neural tube and craniofacial development. However, it is still not clear that which domain(s) of Nog are responsible for proper craniofacial development or neural tube closure. In addition, it is also an important question when, and in what capacity Nog is necessary during development of craniofacial and neural tube.