The zebrafish bobtail mutation abolished the MOCS1 (the molybdenum cofactor synthesis step-1) activity that is required for the posterior body formation and the Fgf/ERK signaling.

The zebrafish bobtail mutation identifies the MOCS1 (the molybdenum cofactor synthesis step-1) gene that is required for the posterior body formation as an essential element of the Fgf/ERK signaling

岸本康之1, 越田澄人2, 古谷-清木 誠3, 川上 厚志4, Reiss Joechen5, 小原 雄治6, 近藤 寿人3,7, 川上 浩一1

1国立遺伝研・初期発生, 2自然機構・岡崎統合バイオ, 3ERATO/SORST・JST, 4東工大・生命理工・生命情報, 5ゲッチンゲン大, 6国立遺伝研, 7阪大・生命機能

Kishimoto Y(1), Koshida S(2), Furutani-Seiki M(3), Kawakami A(4), Reiss J(5), Kohara Y(1), Kondoh H(3,6), Kawakami K(1)

1) National Institute of Genetisc, 2)National Institute of Natural Science, 3)ERATO/SORST JST, 4)Tokyo Institute of Technology, 5)Goettingen Univ., 6)Osaka Univ.

 The formation of vertebrate posterior body and tail requires coordinated growth, differentiation and movement of multipotent progenitor cells located in the tailbud, and is dependent upon the Fgf signaling. Here we describe the zebrafish bobtail (btl) mutation that exhibits a recessive maternal effect, causing a strong reduction of the tail region and abnormal somite patterning. Through positional cloning, we show that the gene mutated in the btl mutant is a zebrafish homologue of the molybdenum cofactor synthesis step-1 (MOCS1) gene. In human, mutations in MOCS1 have been described for a human genetic disorder, molybdenum cofactor deficiency. MOCS1 catalyzes conversion from a guanosine derivative to precursor Z, a biosynthetic intermediate for molybdenum cofactor. Injection of precursor Z at the one-cell stage completely rescued the btl mutant phenotype, demonstrating that the defects in the btl mutant are caused by the lack of precursor Z biosynthesis. Furthermore, we found that phosphorylation of the ERK protein in the tailbud region, which has been shown to be regulated through the Fgf signaling, strongly decreased during gastrulation and segmentation stages in the btl mutant embryos. Implantation of Fgf-soaked beads could not induce ectopic ERK phosphorylation in the btl mutant, indicating that MOCS1 is required for Fgf-dependent ERK activation. Our results suggest a molecular link between molybdenum cofactor biosynthesis and Fgf/ERK signaling during the development of the vertebrate posterior structures.