Genetically defined roles of class I, class Iii, and class Iv Pou domain factors in the development of the mammalian endocrine and nervous systems

Mammalian POU domain proteins are expressed in diverse regions in the developing and adult organism. The patterns of expression suggest roles for class I, class III, and class IV POU domain factors in the development of the neuroendocrine and nervous systems. Indeed, study of the activation, structure, and function of the class I factor, Pit-1, has revealed that it regulates terminal differentiation of three cell phenotypes by regulating classes of genes during anterior pituitary development. Similarly, insights into the roles of class III and class IV POU proteins, suggested through functional studies of class III and class IV protein DNA response elements, have been provided by analysis of genetic models in mice and humans. The consequences of the deletion or natural mutation of these genes are evaluated and compared with observations concerning potential actions of these factors in cell line models. Although the class III and class IV POU domain transcription factors display early patterns of expression in the embryo, genetic evidence demonstrates that their roles are manifested relatively late in development, in the regulation of cell migration, phenotype, and survival.