Expression of didn’t cause a significant change in the expression of any of the assayed genes, even in the presence of its ligand, retinoic acid (39, 65, 66), and so was excluded from further study (Fig

Expression of didn’t cause a significant change in the expression of any of the assayed genes, even in the presence of its ligand, retinoic acid (39, 65, 66), and so was excluded from further study (Fig. Three of these four factors were shown to have corresponding activities in appropriate enhancement or repression of landmark genes in a cell culture model system. These studies identify novel regulators of the somatotropes and lactotropes, and they establish a useful database for further study of these lineages in the anterior pituitary. The differentiation of multiple cell types from a common precursor cell and the subsequent maintenance of distinct cell identities throughout adult life are processes central to most developmental systems (1, 2). A key question in such processes is how a common precursor cell can give rise to multiple cell types with discrete transcriptomic profiles. Cell types differentiating from a common precursor cell must not only activate transcription of genes necessary for the appropriate cell fate, but also repress expression of genes that drive alternate cell identities. The coordination of these regulatory processes requires cell typeCspecific mechanisms of transcriptional control. Additionally, terminally differentiated cells must be subsequently maintained in the differentiated state, necessitating sustained mechanisms and pathways for maintaining cell fate. The establishment and maintenance of cell fate may be regulated by transcription factors that are expressed during development and/or by factors that are induced and sustained during the lifespan of the organism (3, 4). The anterior pituitary is an ideal system for studying mechanisms of lineage establishment and maintenance due to the terminal differentiation and divergence of somatotropes and lactotropes. In mice, the pituitary-specific master regulatory transcription factor POU1F1 is expressed in a subset of developing pituitary cells beginning at embryonic day (e)13.5 (6C8). According to a frequently cited model, these POU1F1+ cells differentiate into the TSH-producing thyrotropes and the GH/prolactin (PRL) dual-expressing somatolactotropes at e16.5 (6, 9). The somatolactotrope precursor then gives rise to the terminally differentiated somatotropes and lactotropes, which produce high levels of GH and PRL protein, respectively (10). Although small populations of somatolactotropes remain present in the pituitaries of adult mice, comprising 1% of all cells in the anterior pituitary, their function remains poorly understood (11, 12). (S)-3-Hydroxyisobutyric acid Additionally, previous studies have found evidence that a subset of lactotropes may derive from a cell with a previous somatotrope identity (13, 14). These findings bring into question the role of the somatolactotrope cells in generating these two terminal lineages and highlight the need to better understand the mechanisms that regulate the somatotrope and lactotrope populations. Despite some questions about the pathway of somatotrope and lactotrope divergence and terminal differentiation, all current models of this pathway agree that expression of is essential to the establishment of both populations of cells and that the somatotrope and lactotrope cells are closely related. In addition to being a master regulator of the somatotrope (S)-3-Hydroxyisobutyric acid and lactotrope lineages, POU1F1 is also a direct activator of both the and genes, and it remains expressed in terminally differentiated somatotropes and lactotropes, driving robust hormone expression throughout adult life (15C18). Despite this expression of in both (S)-3-Hydroxyisobutyric acid cell Itgb5 types, the expression of the (S)-3-Hydroxyisobutyric acid GH and PRL proteins remains primarily restricted to the somatotropes and (S)-3-Hydroxyisobutyric acid lactotropes, respectively (6, 19). This observation suggests the existence of unknown somatotrope- and lactotrope-specific factors that contribute to the divergence and corresponding specificity of gene expression in the two lineages. Several genes have been previously identified as lineage enriched and crucial to the ability of somatotropes and lactotropes to respond to the appropriate physiological signals to secrete their.