Left–right patterning of the mouse lateral plate requires nodal produced in the node

Abstract

Initial determination of left-right (L-R) polarity in mammalian embryos takes place in the node. However, it is not known how asymmetric signals are generated in the node and transferred to the lateral plate mesoderm (LPM). Mice homozygous for a hypomorphic Nodal allele (Nodal(neo)) were generated and found to exhibit L-R defects, including right isomerism. Although the mutant embryos express Nodal at gastrulation stages, the subsequent expression of this gene in the node and left LPM is lost. A transgene that conferred Nodal expression specifically in the node rescued the L-R defects of the Nodal(neo/neo) embryos. Conversely, ectopic expression of the Nodal inhibitor Lefty2 in the node of Nodal(neo/+) embryos resulted in a phenotype similar to that of the Nodal(neo/neo) mutant. These results indicate that Nodal produced in the node is required for expression of Nodal and other left side-specific genes in the LPM.

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

“…7C), in which Nodal protein synthesized in the bilateral PNC domain diffuses as a morphogen to the LPM (Nakamura et al, 2006, Ohi andWright, 2007). Rabbit LP explant cultures isolated before the onset of PNC Nodal transcription never initiated LPM Nodal (not shown), in agreement with corresponding genetic data in mouse (Brennan et al, 2002;Saijoh et al, 2003). In that setting, the role of an inhibitor on both sides falls upon FGF8, which acts to prevent the initiation of the autoregulatory Nodal feedback loop, in which Nodal signaling induces Nodal transcription (Saijoh et al, 2000;Hamada et al, 2002, Ohi andWright, 2007).…”

Massively parallel sequencing identifies the gene Megf8 with ENU-induced mutation causing heterotaxy

“…Genetic analyses have suggested that Nodal expression at the node is required for the activation of left-determinant transcription cascade in the left LPM (15,16). Our data, would suggest the molecular defect underlying the Megf8 m/m phenotype is either an interruption of signal transfer from the node to left LPM and/or a disruption in the initiation and expansion of Nodal expression in the LPM.…”

Xenopus nodal related-1 is indispensable only for left-right axis determination

“…Thus, we can analyze the role of Nodal signaling in the left LPM separately from the Nodal signaling in earlier embryogenesis before neurulation. This "transient signaling" approach offers a concise method for examining the role of Nodal signaling in a distinct phase of embryogenesis, which is comparable to the analysis of the nodespecific nodal hypomorph in mice or southpaw morphants in zebrafish (Feldman et al, 2000;Lowe et al, 2001;Saijoh et al, 2003;Long et al, 2003).…”

“…From these results, Lefty (Antivin) is regarded to act as a midline barrier in order to prevent the diffusive Nodal ligand from functioning on the opposite side (i. e., the right side). Recent studies suggest that, in mouse embryos, nodal expressed in the node induces nodal expression in the left LPM and the two nodal expressing domains cooperatively induce the axial lefty expression Saijoh et al, 2003;Yamamoto et al, 2003).…”