A role for Vg1/Nodal signaling in specification of the intermediate mesoderm

Abstract

SUMMARYThe intermediate mesoderm (IM) is the embryonic source of all kidney tissue in vertebrates. The factors that regulate the formation of the IM are not yet well understood. Through investigations in the chick embryo, the current study identifies and characterizes Vg1/Nodal signaling (henceforth referred to as 'Nodal-like signaling') as a novel regulator of IM formation. Excess Nodal-like signaling at gastrulation stages resulted in expansion of the IM at the expense of the adjacent paraxial mesoderm, whereas inhibition of Nodallike signaling caused repression of IM gene expression. IM formation was sensitive to levels of the Nodal-like pathway co-receptor Cripto and was inhibited by a truncated form of the secreted molecule cerberus, which specifically blocks Nodal, indicating that the observed effects are specific to the Nodal-like branch of the TGFβ signaling pathway. The IM-promoting effects of Nodal-like signaling were distinct from the known effects of this pathway on mesoderm formation and left-right patterning, a finding that can be attributed to specific time windows for the activities of these Nodal-like functions. Finally, a link was observed between Nodal-like and BMP signaling in the induction of IM. Activation of IM genes by Nodal-like signaling required an active BMP signaling pathway, and Nodal-like signals induced phosphorylation of Smad1/5/8, which is normally associated with activation of BMP signaling pathways. We postulate that Nodal-like signaling regulates IM formation by modulating the IM-inducing effects of BMP signaling.

Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos

“…However, Brachyury and BMP4 did induce the expression of neural cell adhesion molecule ( ncam ) (Fig. 5C), as well as markers that are expressed in the MD ( wt1 , pax2 ; Carroll and Vize, 1996; Fleming et al, 2013) and the dorsal aorta ( fli1 , flik1 ; Ciau-Uitz et al, 2000) (Fig. 5D).…”

Late Alk4/5/7 signaling is required for anterior skeletal patterning in sea urchin embryos

“…There are various potential mechanisms by which Univin could enhance nodal expression and function. First, Univin could signal via Smad2/3 to directly promote nodal expression, which is responsive to Smads both in sea urchins and in vertebrates (Penheiter et al, 2002;Tian and Meng, 2006;Nam et al, 2007;Range et al, 2007;Harvey and Smith, 2009;Fleming et al, 2013). Second, Univin and Nodal could signal as heterodimers.…”

The origin of the mammalian kidney: implications for recreating the kidney in vitro

“…During the development of the IM, a low level of BMP signalling is required for the formation of the nephric duct (Obara-Ishihara et al, 1999). In addition to BMP, nodal/activin (ALK4/ACVR1B-mediated signalling) expressed by the LPM is essential for IM specification as its overexpression expands the IM domain in the chick (Fleming et al, 2013). Nodal, which is secreted by the LPM, is antagonized by cerberus 1, which is secreted from the PM, creating a gradient of nodal signalling along M-L axis (Biben et al, 1998).…”