Reciprocal Signaling between the Ectoderm and a Mesendodermal Left-Right Organizer Directs Left-Right Determination in the Sea Urchin Embryo

Abstract

During echinoderm development, expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side, but the mechanisms that restrict nodal expression to the right side are not known. Here we show that establishment of left-right asymmetry in the sea urchin embryo relies on reciprocal signaling between the ectoderm and a left-right organizer located in the endomesoderm. FGF/ERK and BMP2/4 signaling are required to initiate nodal expression in this organizer, while Delta/Notch signaling is required to suppress formation of this organizer on the left side of the archenteron. Furthermore, we report that the H+/K+-ATPase is critically required in the Notch signaling pathway upstream of the S3 cleavage of Notch. Our results identify several novel players and key early steps responsible for initiation, restriction, and propagation of left-right asymmetry during embryogenesis of a non-chordate deuterostome and uncover a functional link between the H+/K+-ATPase and the Notch signaling pathway.

The evolution and conservation of left-right patterning mechanisms

“…If this were the case, this polarization would inevitably result in a leftward fluid flow. Molecular data support our reasoning: manipulation of Notch signaling or of the ion pump ATP4 affects asymmetric Nodal expression in the sea urchin archenteron (Bessodes et al, 2012). A role of Notch in vertebrate LR axis determination has long been known (Krebs et al, 2003;Przemeck et al, 2003).…”

Evolution, divergence and loss of the Nodal signalling pathway: new data and a synthesis across the Bilateria

“…In addition, after gastrulation, nodal expression occurs in different germ layers depending on the group considered: the ectoderm in snails (Grande and Patel 2009), the ectoderm and endoderm in echinoderms (Duboc et al, 2010;Ohguro et al, 2011;Bessodes et al, 2012), all three germ layers in cephalochordates, urochordates, and hemichordates, and the endomesoderm in vertebrates (Hamada et al, 2002;Morokuma et al, 2002;Yu et al, 2002;Duboc et al, 2005;Wlizla 2011). Here we have shown that in brachiopods nodal is restricted to the mesoderm.…”

“…However, unlike vertebrate nodal, which is expressed in the endomesoderm and is involved in its induction, non-vertebrate deuterostome nodal is expressed in different germ layer precursors depending on the group, and does not play a broad role in endoderm and mesoderm specification in all groups. Especially intriguing are results in echinoderms, since nodal and Pitx are expressed in the ectoderm and endoderm (Duboc et al, 2010;Ohguro et al, 2011;Bessodes et al, 2012), and mesoderm cells are specified even when the pathway is blocked (Duboc et al, 2005). In addition, as mentioned above, asymmetric expression and the actions of the Nodal pathway are conserved features of deuterostomes.…”

Nodal signaling regulates specification of ascidian peripheral neurons through control of the BMP signal

“…However, there is relatively little evidence in vertebrates that Nodal signaling governs neural patterning during early development, although it is well known to be essential for specification of primary body axes and for formation of the mesoderm and endoderm (Shen, 2007). Vertebrate Nodal is expressed in the organizer, whereas ascidian and sea urchin Nodal genes are expressed in the ectoderm and endoderm (Bessodes et al, 2012;Chea et al, 2005;Morokuma et al, 2002). In amphioxus, Nodal is also expressed maternally in addition to the zygotical expression in the dorsal blastopore lip that is considered to be the equivalent of vertebrate organizer (Onai et al, 2010;Yu et al, 2007).…”