No abstract

The vertebrate body plan contains both dorsal and ventral midline structures. While dorsal midline structures have been extensively studied, formation of ventral midline structures, and how they become aligned with the dorsal midline, is a fundamental aspect of vertebrate development that is poorly understood. This study uses the chick dorsal mesentery (DM) as a model for investigating the formation of ventral midline structures. We document formation of the DM by epithelial-to-mesenchymal transition (EMT) and medial ingression of the lateral plate coelomic lining and show that DM positioning is a fundamentally dynamic process regulated by relative levels of bone morphogenetic protein (BMP) signaling in the two sides of the ingressing lateral plate. Disruption of this process causes misalignment of the DM and disturbances during initial stages of lung morphogenesis. Since the dorsal midline is a source of BMP antagonists, these results suggest a mechanism for aligning the dorsal and ventral embryonic midlines.

Novel regenerative therapies may stem from deeper understanding of the mechanisms governing cardiovascular lineage diversification. Using enhancer mapping and live imaging in avian embryos, and genetic lineage tracing in mice, we investigated the spatio-temporal dynamics of cardiovascular progenitor populations. We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. Extra-cardiac Nkx2.5 lineage progenitors migrate into the embryo and contribute to clusters of CD41+/CD45+ and RUNX1+ cells in the endocardium, the aorta-gonad-mesonephros region of the dorsal aorta and liver. We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. Taken together, we identified a hemogenic angioblast cell lineage characterized by transient Nkx2.5 expression that contributes to hemogenic endothelium and endocardium, suggesting a novel role for Nkx2.5 in hemoangiogenic lineage specification and diversification.DOI: http://dx.doi.org/10.7554/eLife.20994.001

The nephron is the fundamental structural and functional unit of the kidney. Each mature nephron is patterned along a proximal-distal axis, with blood filtered at the proximal end and urine emerging from the distal end. In order to filter the blood and produce urine, specialized structures are formed at specific proximal-distal locations along the nephron, including the glomerulus at the proximal end, the tubule in the middle and the collecting duct at the distal end. The developmental processes that specify these different nephron segments are not fully understood. Wnt ligands, which are expressed in the nephric duct and later in the nascent nephron itself, are well-characterized inducers of nephrons, and are both required and sufficient for initiation of nephron formation from nephrogenic mesenchyme. Here, we present evidence that Wnt signaling also patterns the proximal-distal nephron axis. Using the chick mesonephros as a model system, a Wnt ligand was ectopically expressed in the coelomic lining, thereby introducing a source of Wnt signaling that is at right angles to the endogenous Wnt signal of the nephric duct. Under these conditions, the nephron axis was re-oriented, such that the glomerulus was always located at a position farthest from the Wnt sources. This re-orientation occurred within hours of exposure to ectopic Wnt signaling, and was accompanied initially by a repression of the early glomerular podocyte markers Wt1 and Pod1, followed by their re-emergence at a position distant from the Wnt signals. Activation of the Wnt signaling pathway in mesonephric explant cultures resulted in strong and specific repression of early and late glomerular markers. Finally, cytoplasmic β-catenin, indicative of active canonical Wnt signaling, was found to be enriched in the distal as compared with the proximal region of the forming nephron. Together, these data indicate that Wnt signaling patterns the proximal-distal axis of the nephron, with glomeruli differentiating in regions of lowest Wnt signaling.

Highlights d Convergence of the coelomic epithelium involves cell flattening and disorganization d Hh signaling regulates coelomic epithelium morphogenesis and N-cadherin distribution d Sec5 and RhoU function downstream of Hh d Hh signaling controls dorsal mesentery midline positioning