The zebrafish cdc73 is essential for embryogenesis and expression of fgf24 in pectoral fin development

Gembu Abe, Tomoya Kotani, Yasuyuki Kishimoto, Koichi Kawakami

(Mol. Dev. Biol., NIG)

  CDC73 is a component of the RNA polymerase II-associated Paf1 complex which has function through transcription at several steps. In human CDC73 is also known as Parafibromin encoded by HRPT2, a tumor suppressor gene implicated in hyperparathyroidism-jaw tumor. While the function through Paf1 complex, a role of CDC73 for the tumorigenesis and also embryonic development in vertebrate remain elusive.
We found zebrafish cdc73 mutant fish in our insertional mutagenesis screen by using the Tol2 transposable element. The cdc73 deficient embryos showed developmental retardation at 18hpf and then embryonic lethality around day4. We analyzed the defects in the mutant in detail and found that the mutants showed the lack of the pectoral fin bud. We then analyzed gene expression patterns. It was revealed that, in the cdc73 mutant, while tbx5 was normally expressed, subsequent fgf24 expression could not be observed. It has been shown that fgf24 is essential for pectoral fin development and its expression is regulated by tbx5. Thus it was suggested that cdc73 functions essential steps to induce fgf24 downstream of tbx5. fgf24 was also expressed in median fin fold regulated by the FGF signaling. We analyzed fgf24 expression in the median fin fold and found that its expression was delayed but not abolished in the mutant. These results indicate that the fgf24 expression is regulated differently and cdc73 specifically affects the expression in the pectoral fin bud. Currently we are analyzing cis-regulatory elements of the fgf24 gene by constructing transgenic fish.

Organogenesis, fin development, cdc73, tbx5, fgf24