Forkhead Factor, FOXL2, in Pituitary Development

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

DESCRIPTION (provided by applicant): Foxl-2 is expressed in the developing eye and in the adult ovary and is required for normal development and function of these organs in humans. Recently, expression of FoxL2 has been detected in the developing mouse pituitary from e10.5 to el 5. To examine the role of FOXL2 in pituitary development, the following studies will be performed: characterize the developmental expression of Foxl2 and place it in the genetic hierarchy of pituitary developmental control, define important regulatory sequences for Foxl2 expression in cell culture and transgenic mice, and examine the role of FOXL2 in the developing anterior pituitary by generation of gain and loss of function alleles. In situ hybridization of pituitaries from normal mice will be used to characterize Foxl2 expression. Normal expression patterns for Foxl2 will be compared to those in mice with mutations in critical pituitary transcription factors. This information will place FOXL2 in the genetic hierarchy. Transient transfections of mammalian cells and electrophoretic mobility shift assays will be used to define the minimal essential sequence for Foxl2 expression and to test for direct regulation by factors that are upstream of Foxl2 in the genetic hierarchy. These findings will be confirmed in transgenic animals. To delineate the role of FOXL2 in pituitary development, FoxL2 will be over-expressed and will be disrupted specifically in the pituitaries of mice, allowing us to separate the role of FOXI.2 in the pituitary from its role in other organs.