Eya1 is required for lineage-specific differentiation, but not for cell survival in the zebrafish adenohypophysis

Nica, G., Herzog, W., Sonntag, C., Nowak, M., Schwarz, H., Zapata, A.G., Hammerschmidt, M.
Developmental Biology   292(1): 189-204 (Journal)
Registered Authors
Hammerschmidt, Matthias, Herzog, Wiebke, Nica, Gabriela, Nowak, Matthias, Sonntag, Carmen
eya1, six1, Adenohypophysis, aal, dog, Zebrafish, Cell differentiation, Apoptosis
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Apoptosis/genetics
  • Apoptosis/physiology
  • Cell Differentiation/genetics
  • Cell Differentiation/physiology*
  • Cell Lineage/genetics
  • Cell Lineage/physiology*
  • Cell Survival/genetics
  • Cell Survival/physiology
  • Gene Expression Regulation, Developmental/physiology
  • Growth Hormone/biosynthesis
  • Growth Hormone/genetics
  • Homeodomain Proteins/biosynthesis
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/physiology
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/physiology*
  • LIM-Homeodomain Proteins
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins/biosynthesis
  • Nerve Tissue Proteins/genetics
  • Nuclear Proteins/genetics
  • Nuclear Proteins/physiology*
  • Pituitary Gland, Anterior/cytology*
  • Pituitary Gland, Anterior/embryology*
  • Pro-Opiomelanocortin/biosynthesis
  • Pro-Opiomelanocortin/genetics
  • Protein Tyrosine Phosphatases/genetics
  • Protein Tyrosine Phosphatases/physiology*
  • Thyrotropin/biosynthesis
  • Thyrotropin/genetics
  • Transcription Factor Pit-1/biosynthesis
  • Transcription Factor Pit-1/genetics
  • Transcription Factors/biosynthesis
  • Transcription Factors/genetics
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
16458879 Full text @ Dev. Biol.
The homeodomain transcription factor Six1 and its modulator, the protein phosphatase Eya1, cooperate to promote cell differentiation and survival during mouse organ development. Here, we studied the effects caused by loss of eya1 and six1 function on pituitary development in zebrafish. eya1 and six1 are co-expressed in all adenohypophyseal cells. Nevertheless, eya1 (aal, dog) mutants show lineage-specific defects, defining corticotropes, melanotropes, and gonadotropes as an Eya1-dependent lineage, which is complementary to the Pit1 lineage. Furthermore, eya1 is required for maintenance of pit1 expression, leading to subsequent loss of cognate hormone gene expression in thyrotropes and somatotropes of mutant embryos, whereas prolactin expression in lactotropes persists. In contrast to other organs, adenohypophyseal cells of eya1 mutants do not become apoptotic, and the adenohypophysis remains at rather normal size. Also, cells do not trans-differentiate, as in the case of pit1 mutants, but display morphological features characteristic for nonsecretory cells. Some of the adenohypophyseal defects of eya1 mutants are moderately enhanced in combination with antisense-mediated loss of Six1 function, which per se does not affect pituitary cell differentiation. In conclusion, this is the first report of an essential role of Eya1 during pituitary development in vertebrates. Eya1 is required for lineage-specific differentiation of adenohypophyseal cells, but not for their survival, thereby uncoupling the differentiation-promoting and anti-apoptotic effects of Eya proteins seen in other tissues.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes