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Development June 1, 2013; 140 (11): 2334-44.

Maternal Dead-End1 is required for vegetal cortical microtubule assembly during Xenopus axis specification.

Mei W , Jin Z , Lai F , Schwend T , Houston DW , King ML , Yang J .

Vertebrate axis specification is an evolutionarily conserved developmental process that relies on asymmetric activation of Wnt signaling and subsequent organizer formation on the future dorsal side of the embryo. Although roles of Wnt signaling during organizer formation have been studied extensively, it is unclear how the Wnt pathway is asymmetrically activated. In Xenopus and zebrafish, the Wnt pathway is triggered by dorsal determinants, which are translocated from the vegetal pole to the future dorsal side of the embryo shortly after fertilization. The transport of dorsal determinants requires a unique microtubule network formed in the vegetal cortex shortly after fertilization. However, molecular mechanisms governing the formation of vegetal cortical microtubule arrays are not fully understood. Here we report that Dead-End 1 (Dnd1), an RNA-binding protein required for primordial germ cell development during later stages of embryogenesis, is essential for Xenopus axis specification. We show that knockdown of maternal Dnd1 specifically interferes with the formation of vegetal cortical microtubules. This, in turn, impairs translocation of dorsal determinants, the initiation of Wnt signaling, organizer formation, and ultimately results in ventralized embryos. Furthermore, we found that Dnd1 binds to a uridine-rich sequence in the 3''-UTR of trim36, a vegetally localized maternal RNA essential for vegetal cortical microtubule assembly. Dnd1 anchors trim36 to the vegetal cortex in the egg, promoting high concentrations of Trim36 protein there. Our work thus demonstrates a novel and surprising function for Dnd1 during early development and provides an important link between Dnd1, mRNA localization, the microtubule cytoskeleton and axis specification.

PubMed ID: 23615278
PMC ID: PMC3653556
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: acta4 actc1 actl6a bicc1 chrd.1 dnd1 fbxo5 gdf1 krt12.4 msx1 nanos1 ncam1 nodal3.1 nodal3.2 nog odc1 prl.2 sia1 szl tcf7l1 trim36 vegt ventx1.2 ventx2.2 wnt11 wnt8a
GO keywords: germ cell development [+]
Antibodies: Dnd1 Ab1 Trim36 Ab1 Tubb3 Ab2

Article Images: [+] show captions
References [+] :
Aramaki, Molecular cloning and expression of dead end homologue in chicken primordial germ cells. 2007, Pubmed, Xenbase