Park & Jameson 05

Park & Jameson 05 - 0013-7227/05/$15.00/0 Printed...

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Minireview: Transcriptional Regulation of Gonadal Development and Differentiation Susan Y. Park and J. Larry Jameson Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611 Theembryonicgonadisundifferentiatedinmalesandfemales until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the mo- lecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferoustubuleswherespermatogenesisoccurs.TheLey- dig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are sur- rounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathwaysprovidesthefoundationforunderstandingthiscrit- ical developmental event and provides new insight into the causes of gonadal dysgenesis. ( Endocrinology 146: 1035–1042, 2005) L IKE MOST ORGAN systems, mammalian gonadal de- velopment involves a complex interplay of multiple cell types, and it occurs during a relatively narrow time window. Thus, it is important to understand the temporal pattern of gene expression as well as the spatial relationships of the developing tissues. For these reasons, most recent studies have used the mouse as a model for examining go- nadal development because it is amenable to genetic ma- nipulation as well as detailed histologic and biochemical characterization. During the transition from an undifferen- tiated gonad to a testis or ovary, the female and male gonad each display characteristic morphological features and pat- terns of gene expression (1). The coordinated differentiation of the embryonic urogenital ridge, from the bipotential state to sexual dimorphism, provides an opportunity to identify the key factors and commitment steps that underlie gonadal differentiation (2). In humans, the functional significance of some of these molecules is evident from mutations that impair gonadal development and reproduction (3–5). For example, deletions of the Y chromosomal gene, SRY (sex-determining region on the Y chromosome) cause XY male-to-female sex reversal, whereas SRY translocations to the X chromosome lead to XX
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This note was uploaded on 05/19/2011 for the course ZOO 4926 taught by Professor Staff during the Summer '08 term at University of Florida.

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Park & Jameson 05 - 0013-7227/05/$15.00/0 Printed...

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