Intermediate mesoderm
Intermediate mesoderm or intermediate mesenchyme is a narrow section of the mesoderm (one of the three primary germ layers) located between the paraxial mesoderm and the lateral plate of the developing embryo. The intermediate mesoderm develops into vital parts of the urogenital system (kidneys, gonads and respective tracts). Early formation Factors regulating the formation of the intermediate mesoderm are not fully understood. It is believed that bone morphogenic proteins, or BMPs, specify regions of growth along the dorsal-ventral axis of the mesoderm and plays a central role in formation of the intermediate mesoderm. Vg1/Nodal signalling is an identified regulator of intermediate mesoderm formation acting through BMP signalling. Excess Vg1/Nodal signalling during early gastrulation stages results in expansion of the intermediate mesoderm at the expense of the adjacent paraxial mesoderm, whereas inhibition of Vg1/Nodal signalling represses intermediate mesoderm formation. A link has been established between Vg1/Nodal signalling and BMP signalling, whereby Vg1/Nodal signalling regulates intermediate mesoderm formation by modulating the growth-inducing effects of BMP signalling. Other necessary markers of intermediate mesoderm induction include the odd-skipped related gene (Osr1) and paired-box-2 gene (Pax2) which require intermediate levels of BMP signalling to activate Markers of early intermediate mesoderm formation are often not exclusive to the intermediate mesoderm. This can be seen in early stages of intermediate mesoderm differentiation where higher levels of BMP stimulate growth of lateral plate tissue, whilst lower concentrations lead to paraxial mesoderm and somite formation. Osr1, which encodes a zinc-finger DNA-binding protein, and LIM-type homeobox gene (Lhx1) expression overlaps the intermediate mesoderm as well as the lateral plate. Osr1 has expression domains encompassing the entire length of the anterior-posterior (AP) axis from the first somites. It is not until the 4th-8th somite stage that markers with greater specificity to the intermediate mesoderm are identified including Pax2/8 genes activated from the 6th somite (Bouchard, 2002). Lhx1 expression also becomes more restricted to the intermediate mesoderm. Genetic analyses in animal studies show that Lhx1, Osr1 and Pax2/8 signalling are all critical in specification of the intermediate mesoderm into its early derivatives. Derived organs and tissues As development proceeds, the intermediate mesoderm differentiates sequentially along the anterior-posterior axis into three successive stages of the early mammalian and avian urogenital system, named pronephros, mesonephros and metanephros respectively (anamniote embryos form only a pronephros and mesonephros). The intermediate mesoderm will eventually develop into the kidney and parts of both male and female reproductive systems. Kidneys Early kidney structures include the pronephros and mesonephros, whose complexity, size and duration can vary greatly between vertebrate species. The adult kidney, also referred to as the metanephric kidney, forms at the posterior end of the intermediate mesoderm after the degeneration of previous, less complex kidney structures. Pronephros During early development (approximately day 22 in humans), the pronephric duct forms from the intermediate mesoderm, ventral to the anterior somites. The cells of the pronephric duct migrate caudally whilst inducing adjacent mesenchyme to form the tubules of the initial kidney-like structure called the pronephros. This process is regulated by Pax2/8