A β-catenin gradient links the clock and wavefront systems in mouse embryo segmentation

Abstract

Rhythmic production of vertebral precursors, the somites, causes bilateral columns of embryonic segments to form. This process involves a molecular oscillator--the segmentation clock--whose signal is translated into a spatial, periodic pattern by a complex signalling gradient system within the presomitic mesoderm (PSM). In mouse embryos, Wnt signalling has been implicated in both the clock and gradient mechanisms, but how the Wnt pathway can perform these two functions simultaneously remains unclear. Here, we use a yellow fluorescent protein (YFP)-based, real-time imaging system in mouse embryos to demonstrate that clock oscillations are independent of beta-catenin protein levels. In contrast, we show that the Wnt-signalling gradient is established through a nuclear beta-catenin protein gradient in the posterior PSM. This gradient of nuclear beta-catenin defines the size of the oscillatory field and controls key aspects of PSM maturation and segment formation, emphasizing the central role of Wnt signalling in this process.

FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

“…3 G-J), suggesting that the WNT pathway is downstream of FGF signaling. Conversely, loss of WNT signaling, which similarly halts axis extension and somitogenesis, reciprocally results in the loss of FGF gene expression (13,16). This reciprocal and complementary down-regulation prevents the determination of which signal is the wavefront.…”

“…WNT signaling has also been proposed to contribute to wavefront activity (13,14). Manipulation of canonical WNT signaling also causes corresponding shifts in the determination front (13,15,16).…”

“…Manipulation of canonical WNT signaling also causes corresponding shifts in the determination front (13,15,16). However, in WNT loss-of-function embryos, FGF signaling is also affected.…”

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

“…During early animal embryogenesis, β-catenin specifies the site of endoderm internalization and promotes posterior fates in most studied systems (Byrum and Wikramanayake, 2013;Darras et al, 2011;Haegel et al, 1995;Henry et al, 2008;Lee et al, 2006;Logan et al, 1999;Srivastava et al, 2014;Wikramanayake et al, 2003). In later stages of development, the canonical Wnt pathway influences the formation of multiple cell types, tissues and organ systems (Aulehla et al, 2008;Grigoryan et al, 2008;Hari et al, 2002;Holland et al, 2005;Kiecker and Niehrs, 2001; Lewis et al, 2004;Petersen and Reddien, 2009a;Schneider and Bowerman, 2007;Tan et al, 2006;Watanabe et al, 2014), and most prominently, the anteroposterior (AP) patterning of the vertebrate central nervous system (Ciani and Salinas, 2005). In adult organisms β-catenin is essential for tissue homeostasis and its deregulation leads to degenerative diseases and cancers (Clevers and Nusse, 2012).…”

Wnt Signaling in Mammalian Development: Lessons from Mouse Genetics

“…Secondly, a gradient of Wnt signaling activity, likely established by the graded expression of Wnt3a along the A-P axis, is thought to constitute part of the "determination wavefront" that positions the segmentation boundary during somitogenesis (Pourquie 2011). By manipulating Wnt activity gradient using b-catenin LOF and GOF mutants, studies show that high level Wnt activity maintains posterior PSM in an undifferentiated state permissive of Notch signaling oscillation, while a gradual reduction of Wnt activity in the anterior PSM sets the boundary to arrest Notch signaling oscillation and to activate genes required for segment formation (Aulehla et al 2008;Dunty et al 2008). Wnt3a is also required for left-right (L-R) axis determination because Wnt3a null mutants display laterality defects in multiple visceral organs (Nakaya et al 2005).…”