greb1 regulates convergent extension movement and pituitary development in zebrafish.

greb1, growth regulation by estrogen in breast cancer 1, is an important estrogen response gene, which participates in breast cancer formation. However, the role of greb1 in development is largely unknown. In this study, we have characterized greb1 expression patterns and revealed its regulative role in convergent extension movement and pituitary development in zebrafish. In zebrafish adults, greb1 was revealed to be expressed mainly in pituitary, hypothalamus, liver, and gonads. During embryogenesis, RT-PCR and WISH revealed its spatial and temporal expression specific to embryonic margin during gastrulation, central nervous system during segmentation and brain ventricular regions from 24hpf. To investigate its function, we utilized TALEN-mediated knockout strategy and obtained a greb1 mutant zebrafish line. greb1 mutation caused convergent extension (CE) movement defect and developmental delay during gastrulation, and resulted in significant growth defects in zebrafish adults. Moreover, four pituitary cells including somatotropes, thyrotropes, lactotropes and gonadotropes were specifically reduced during embryogenesis. Importantly, pituitary hormones-encoding genes and their serum products, such as GH, TSH, PRL, FSH, and LH, were severely diminished in greb1 mutants, and high mortality and significant growth defects were observed. Therefore, our present study indicates that greb1 is a novel regulator for CE movement and pituitary development in zebrafish.

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