This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herzog, W. Articles by Hammerschmidt, M. Search for Related Content PubMed PubMed Citation Articles by Herzog, W. Articles by Hammerschmidt, M.

Genetic Analysis of Adenohypophysis Formation in Zebrafish

Max-Planck Institute for Immunobiology (W.H., C.S., M.H.), 79108 Freiburg, Germany; Exelixis Germany (B.W., J.O.), 72076 Tuebingen, Germany; and Max-Planck Institute for Developmental Biology (H.-M.M.), 72076 Tuebingen, Germany

Address all correspondence and requests for reprints to: Matthias Hammerschmidt, Max-Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany. E-mail: hammerschmid{at}immunbio.mpg.de.

The adenohypophysis consists of at least six different cell types, somatotropes, lactotropes, thyrotropes, melanotropes, corticotropes, and gonadotropes. In mouse, cloning of spontaneous mutations and gene targeting has revealed multiple genes required for different steps of adenohypophysis development. Here, we report the results of a systematic search for genes required for adenohypophysis formation and patterning in zebrafish. By screening F3 offspring of N-ethyl-N-nitrosourea-mutagenized founder fish, we isolated eleven mutants with absent or reduced expression of GH, the product of somatotropes, but a normally developing hypothalamus. Of such mutants, eight were further analyzed and mapped. They define four genes essential for different steps of adenohypophysis development. Two of them, lia and pia, affect the entire adenohypophysis, whereas the other two are required for a subset of adenohypophyseal cell types only. The third gene is zebrafish pit1 and is required for lactotropes, thyrotropes, and somatotropes, similar to its mouse ortholog, whereas the fourth, aal, is required for corticotropes, melanotropes, thyrotropes, and somatotropes, but not lactotropes. In conclusion, the isolated zebrafish mutants confirm principles of adenohypophysis development revealed in mouse, thereby demonstrating the high degree of molecular and mechanistic conservation among the different vertebrate species. In addition, they point to thus far unknown features of adenohypophysis development, such as the existence of a new lineage of pituitary cells, which partially overlaps with the Pit1 lineage. Positional cloning of the lia, pia, and aal genes might reveal novel regulators of vertebrate pituitary development.

This article has been cited by other articles:

				B. V. Fausett, J. D. Gumerson, and D. Goldman The Proneural Basic Helix-Loop-Helix Gene Ascl1a Is Required for Retina Regeneration J. Neurosci., January 30, 2008; 28(5): 1109 - 1117. [Abstract] [Full Text] [PDF]

				X. Zhu, A. S. Gleiberman, and M. G. Rosenfeld Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks Physiol Rev, July 1, 2007; 87(3): 933 - 963. [Abstract] [Full Text] [PDF]

				T. T. To, S. Hahner, G. Nica, K. B. Rohr, M. Hammerschmidt, C. Winkler, and B. Allolio Pituitary-Interrenal Interaction in Zebrafish Interrenal Organ Development Mol. Endocrinol., February 1, 2007; 21(2): 472 - 485. [Abstract] [Full Text] [PDF]

				I M McGonnell and R C Fowkes Fishing for gene function - endocrine modelling in the zebrafish. J. Endocrinol., June 1, 2006; 189(3): 425 - 439. [Abstract] [Full Text] [PDF]

				N.-A. Liu, Q. Liu, K. Wawrowsky, Z. Yang, S. Lin, and S. Melmed Prolactin Receptor Signaling Mediates the Osmotic Response of Embryonic Zebrafish Lactotrophs Mol. Endocrinol., April 1, 2006; 20(4): 871 - 880. [Abstract] [Full Text] [PDF]

				H.-M. Pogoda, S. von der Hardt, W. Herzog, C. Kramer, H. Schwarz, and M. Hammerschmidt The proneural gene ascl1a is required for endocrine differentiation and cell survival in the zebrafish adenohypophysis Development, March 15, 2006; 133(6): 1079 - 1089. [Abstract] [Full Text] [PDF]

				W. Herzog, C. Sonntag, S. von der Hardt, H. H. Roehl, Z. M. Varga, and M. Hammerschmidt Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis Development, August 1, 2004; 131(15): 3681 - 3692. [Abstract] [Full Text] [PDF]

				G. Nica, W. Herzog, C. Sonntag, and M. Hammerschmidt Zebrafish pit1 Mutants Lack Three Pituitary Cell Types and Develop Severe Dwarfism Mol. Endocrinol., May 1, 2004; 18(5): 1196 - 1209. [Abstract] [Full Text] [PDF]