Eya1 is required for lineage-specific differentiation, but not for cell survival in the zebrafish adenohypophysis.
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.
Nica
Gabriela
G
Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Herzog
Wiebke
W
Sonntag
Carmen
C
Nowak
Matthias
M
Schwarz
Heinz
H
Zapata
Agustin G
AG
Hammerschmidt
Matthias
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000196:embryology*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D013972:Thyrotropin / Q000096:biosynthesis / Q000235:genetics; D050817:Transcription Factor Pit-1 / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C498351:Six1 protein, zebrafish; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D029961:Zebrafish Proteins; C433629:homeobox protein PITX3; C110148:lhx3 protein, zebrafish; D011333:Pro-Opiomelanocortin; D013972:Thyrotropin; D013006:Growth Hormone; D017027:Protein Tyrosine Phosphatases; C501158:eya1 protein, zebrafish