XB-ART-6225Development December 1, 2002; 129 (24): 5815-25.
Neural tube closure requires Dishevelled-dependent convergent extension of the midline.
In Xenopus, Dishevelled (Xdsh) signaling is required for both neural tube closure and neural convergent extension, but the connection between these two morphogenetic processes remains unclear. Indeed normal neurulation requires several different cell polarity decisions, any of which may require Xdsh signaling. In this paper we address two issues: (1) which aspects of normal neurulation require Xdsh function; and (2) what role convergent extension plays in the closure of the neural tube. We show that Xdsh signaling is not required for neural fold elevation, medial movement or fusion. Disruption of Xdsh signaling therefore provides a specific tool for uncoupling convergent extension from other processes of neurulation. Using disruption of Xdsh signaling, we demonstrate that convergent extension is crucial to tube closure. Targeted injection revealed that Xdsh function was required specifically in the midline for normal neural tube closure. We suggest that the inherent movement of the neural folds can accomplish only a finite amount of medial progress and that convergent extension of the midline is necessary to reduce the distance between the nascent neural folds, allowing them to meet and fuse. Similar results with Xenopus strabismus implicate the planar cell polarity (PCP) signaling cascade in neural convergent extension and tube closure. Together, these data demonstrate that PCP-mediated convergent extension movements are crucial to proper vertebrate neurulation.
PubMed ID: 12421719
Article link: Development
Genes referenced: ascl2 ascl3 dvl1 dvl2 foxd4l1.2 fubp1 ntn1 pax3 shh sox2 vangl2
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|Fig. 7. Persistent failure of midline neural convergent extension in Xdd1 injected embryos. (A) Control embryos stained for Xfd12 expression at stage 10.5. (B) Xdd1-injected embryos stained for Xfd12 at stage 10.5. (C) Control embryos stained for Xfd12 expression at stage 11.5. (D) Xdd1-injected embryos stained for Xfd12 at stage 11.5. (E) Expression of Xnetrin in control embryo at mid-neurulation. (F) Expression of Xnetrin in two Xdd1-injected embryos at mid-neurulation; green arrow indicates gap in Xnetrin expression domain. (G) Expression of Xnetrin in control embryo at late neurulation. (H) Expression of Xnetrin in two Xdd1-injected embryos at late neurulation; green arrow indicates gap in Xnetrin expression domain; red arrow indicates area at posterior floor of the open NT, which does not express Xnetrin. (I) Expression of SHH in control embryo at late neurulation (embryo has been cleared). (J) Expression of SHH in two Xdd1-injected embryos at late neurulation; green arrow indicates gap in SHH expression domain; red arrow indicates area in the floor of the open NT, which does not express SHH.|
|Fig. 8. Xdd1 disrupts convergent extension of dorsolateral neural tissue. (A) Dorsal view Xpax3 expression (blue staining) in a control embryo at mid-neurula stage. (B) Xpax3 expression at mid-neurulation in an embryo injected with Xdd1. It should be noted that embryological and fate-mapping experiments have identified an additional convergent extension event which shapes the dorsal neural tube following overt tube closure (Davidson and Keller, 1999). This later convergent extension event was also disrupted by expression of Xdd1 (not shown). (C) Expression of Xash3 in a control embryo. (D) Expression of Xash3 in an Xdd1-injected embryo; the expression domains are foreshortened. (E) Expression of Sox2 in a control embryo at stage 14. (F) Expression pattern of Sox2 in Xdd1-injected embryos. As a control, we targeted Xdd1 injections to the dorsal, vegetal blastomeres, where expression inhibits predominantly mesodermal convergent extension and does not inhibit NT closure (Wallingford and Harland, 2001); in those embryos, Sox2 expression resembled wild type (not shown).|
|Fig. 9. Expression of wild-type Stbm elicits neural tube closure defects and failure of neural convergent extension. (A) Control embryo at mid-neurulation with closing NT. (B) Stbm-injected embryo with defective NT closure. (C) Xfd12 expression in control embryo at stage 14. (D) Xfd12 expression reveals defective neural convergent extension in a stage 14 Stbm-injected embryo. (E) Expression of Xpax3 in a control embryo. (F) Expression of Xpax3 in an XStbm injected embryo. (G) Expression of Xash3 in a control embryo. (H) Expression of Xash3 in an XStbm-injected embryos. (I) Expression of Sox2 in a control embryo. (J) Expression of Sox2 in an XStbm-injected embryos.|
|ascl3 (achaete-scute complex homolog 3) gene expression in Xenopus laevis embryos, NF stage 18, as assayed by in situ hybridization. dorsal view: anterior left.|