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      Genetic regulation of murine pituitary development

      review-article
      Journal of Molecular Endocrinology
      Bioscientifica Ltd
      pituitary, developmental factors, morphogenesis, stem cell

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          Abstract

          Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection of the molecular mechanisms controlling patterning of the ventral diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch. There is also a better characterisation of processes that underlie maintenance of pituitary progenitors, specification of endocrine lineages and the three-dimensional organisation of newly differentiated endocrine cells. Furthermore, a population of adult pituitary stem cells (SCs), originating from embryonic progenitors, have been described and shown to have not only regenerative potential, but also the capacity to induce tumour formation. Finally, the successful recapitulation in vitro of embryonic events leading to generation of endocrine cells from embryonic SCs, and their subsequent transplantation, represents exciting advances towards the use of regenerative medicine to treat endocrine deficits. In this review, an up-to-date description of pituitary morphogenesis will be provided and discussed with particular reference to pituitary SC studies.

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          Most cited references122

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          Evolution of the cancer stem cell model.

          Genetic analyses have shaped much of our understanding of cancer. However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells (CSCs) can drive tumor growth. Although often considered as mutually exclusive models to describe tumor heterogeneity, we propose that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and nongenetic influences in contributing to tumor heterogeneity. We offer an approach to integrating CSCs and cancer genetic data that will guide the field in interpreting past observations and designing future studies. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.

            In mammals, the transcription factor SRY, encoded by the Y chromosome, is normally responsible for triggering the indifferent gonads to develop as testes rather than ovaries. However, testis differentiation can occur in its absence. Here we demonstrate in the mouse that a single factor, the forkhead transcriptional regulator FOXL2, is required to prevent transdifferentiation of an adult ovary to a testis. Inducible deletion of Foxl2 in adult ovarian follicles leads to immediate upregulation of testis-specific genes including the critical SRY target gene Sox9. Concordantly, reprogramming of granulosa and theca cell lineages into Sertoli-like and Leydig-like cell lineages occurs with testosterone levels comparable to those of normal XY male littermates. Our results show that maintenance of the ovarian phenotype is an active process throughout life. They might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.
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              Notch signaling at a glance.

              Cell-cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.
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                Author and article information

                Journal
                J Mol Endocrinol
                J. Mol. Endocrinol
                JME
                Journal of Molecular Endocrinology
                Bioscientifica Ltd (Bristol )
                0952-5041
                1479-6813
                April 2015
                13 January 2015
                : 54
                : 2
                : R55-R73
                Affiliations
                [1]Division of Stem Cell Biology and Developmental Genetics, MRC National Institute for Medical Research , The Ridgeway, Mill Hill, London, NW7 1AA, UK
                Author notes
                Correspondence should be addressed to K Rizzoti; Email: krizzot@ 123456nimr.mrc.ac.uk
                Article
                JME140237
                10.1530/JME-14-0237
                4335376
                25587054
                f892c791-9d55-459d-b4df-0a46191d27dd
                © 2015 The authors

                This work is licensed under a Creative Commons Attribution 3.0 Unported License

                History
                : 4 December 2014
                : 7 January 2015
                Categories
                Review

                Endocrinology & Diabetes
                pituitary,developmental factors,morphogenesis,stem cell
                Endocrinology & Diabetes
                pituitary, developmental factors, morphogenesis, stem cell

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