PUBLICATION
Zebrafish pit1 mutants lack three pituitary cell types and develop severe dwarfism
- Authors
- Nica, G., Herzog, W., Sonntag, C., and Hammerschmidt, M.
- ID
- ZDB-PUB-040304-3
- Date
- 2004
- Source
- Molecular endocrinology (Baltimore, Md.) 18(5): 1196-1209 (Journal)
- Registered Authors
- Hammerschmidt, Matthias, Herzog, Wiebke, Nica, Gabriela, Sonntag, Carmen
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics*
- Cell Lineage/genetics
- DNA-Binding Proteins/metabolism*
- Dwarfism/genetics*
- Embryo, Nonmammalian/cytology
- Gene Expression Regulation, Developmental/physiology
- Genetic Techniques
- Homeodomain Proteins/metabolism
- Mutation/genetics
- Pituitary Gland, Anterior/embryology*
- Transcription Factor Pit-1
- Transcription Factors/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 14988429 Full text @ Mol. Endocrinol.
Citation
Nica, G., Herzog, W., Sonntag, C., and Hammerschmidt, M. (2004) Zebrafish pit1 mutants lack three pituitary cell types and develop severe dwarfism. Molecular endocrinology (Baltimore, Md.). 18(5):1196-1209.
Abstract
The Pou domain transcription factor Pit-1 is required for lineage determination and cellular commitment processes during mammalian adenohypophysis development. Here we report the cloning and mutational analysis of a pit1 homologue from zebrafish. Compared with mouse, zebrafish pit1 starts to be expressed at a much earlier stage of adenohypophysis development. However, like in mouse, expression is restricted to a subset of pituitary cell types, excluding proopiomelanocortin (pomc)-expressing cells (corticotropes, melanotropes) and possibly gonadotropes. We could identify two ENU-induced zebrafish pit1 null mutants. Most mutants die during larval stages, while survivors develop severe dwarfism. Mutant larvae lack lactotropes, somatotropes and thyrotropes, although the adenohypophysis is of normal size, without any sign of increased apoptosis rates. Instead, mutant embryos initiate ectopic expression of pomc in pit1-positive cells, leading to an expansion of the Pomc lineage. Similarly, the number of gonadotropes seems increased, as indicated by the expression of gsualpha, a marker for thyrotropes and gonadotropes. In pit1 mutants, the total number of gsualpha-positive cells is normal despite the loss of gsualpha and tshbeta co-expressing cells. Together, these data suggest a transfating of the Pit1 lineage to the Pomc and possibly the gonadotroph lineages in the mutant, and a pomc- and gonadotropin-repressive role of Pit1 during normal zebrafish development. This is different from mouse, for which a repressive role of Pit-1 has only been reported for the gonadotropin Lhbeta, but not for Pomc. In sum, our data point to both conserved and class-specific aspects of Pit1 function during pituitary development in different vertebrate species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping