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Submitted on September 26, 2003
Accepted on January 21, 2004
Max-Planck Institute for Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany; Exelixis Germany, Spemannstrasse 35, 72076 Tuebingen, Germany; Max-Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tuebingen, Germany
* To whom correspondence should be addressed. 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 ENU-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, while 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 orthologue, while 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.
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