Manifold functions of the Nail-Patella Syndrome gene Lmx1b in vertebrate development.

The LIM (Lin-1, Isl-1 and Mec-3)-homeodomain transcription factor 1 beta (Lmx1b) is widely expressed in vertebrate embryos, and is implicated in the development of diverse structures such as limbs, kidneys, eyes and brains. LMX1B mutations in humans cause an autosomal dominant inherited disease called nail-patella syndrome (NPS), which is characterized by abnormalities of the arms and legs as well as kidney disease and glaucoma. Expression of Lmx1b in the dorsal compartment of growing limb buds is critical for specification of dorsal limb cell fates and consequently dorsoventral patterning of limbs. In addition, Lmx1b is involved in the differentiation of anterior eye structures, formation of the glomerular basement membrane in kidneys and development of the skeleton, especially calvarial bones. In the central nervous system, Lmx1b controls the inductive activity of isthmic organizer, differentiation and maintenance of central serotonergic neurons, as well as the differentiation and migration of spinal dorsal horn neurons. Although details of the genetic programs involved in these developmental events are largely unknown, it is suggested that Lmx1b plays central roles in fate determination or cell differentiation in these tissues. Sustained expression of Lmx1b in the postnatal and mature mouse brain suggests that it also plays important roles in brain maturation and in the regulation of normal brain functions. This review aims to highlight recent insights into the many activities of Lmx1b in vertebrates.