“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms.

Oxygen deprived (The zebrafish embryo as a dynamic model of anoxia tolerance by Bryce A. Mendelsohn, Bethany L. Kassebaum, and Jonathan D. Gitlin, Dev Dyn237:1780–1788; and Coordination of development and metabolism in the pre-midblastula transition zebrafish embryo by Bryce A. Mendelsohn and Jonathan D. Gitlin, Dev Dyn237:1789–1798) It is hard to grow when you cannot breath—consequently, zebrafish embryos postpone development in an anoxic environment. Depending on the embryonic stage and the metabolic state, development proceeds when oxygen becomes available. The authors characterized this intriguing tolerance phenomenon in back-to-back studies. One question addressed is, how might anoxia trigger arrest? Mendelsohn, Kassebaum, and Gitilin tested if energy homeostasis was involved. The 24-hour-old embryos were incubated in normal oxygen with chemicals such as cyanide that block oxidative phosphorylation—causing a shift from aerobic to anaerobic energy production. This shift, leads to developmental arrest similar to that seen under anoxic conditions. What mechanism is involved in sensing the change in energy metabolism? One contender is the energy sensing AMP activated protein kinase (AMPK) pathway. Consistent with this supposition, the authors show, using phosphorylation assays, that AMPK and downstream factors are activated in embryos exposed to anoxia or inhibitors of oxidative phosphorylation. In their second study, Mendelsohn and Gitilin show that younger embryos also stall development upon chemical induced anoxia. Developmental arrest was initiated before the mid blastula transition, when maternal components rule, revealing that in this case zygotic transcription is not required. Maternal AMPK is activated by anoxia, suggesting a conservation of response between young and old embryos. The AMPK pathway regulates essential processes including translation, cell cycle control, and glycolysis that are required for development to proceed making the pathway a good candidate for the link from energy sensing to anoxia tolerance.

Sympathetic development (Loss of the Prader-Willi Syndrome protein necdin causes defective migration, axonal outgrowth, and survival of embryonic sympathetic neurons by Alysa A. Tennese, Christopher B. Gee, and Rachel Wevrick, Dev Dyn237:1935–1943) Prader-Willi syndrome is a neurodevelopmental disorder with multiple symptoms including low muscle tone, learning disability, excessive hunger leading to obesity, and difficulty swallowing. The disease is caused by deletion of several imprinted genes on chromosome 15. One, Ndn, encodes necdin—a protein previously shown in mice to be required for normal development of sensory and central neurons. Tennese, Gee, and Wevrick now show that Ndn knock out mice also have developmental defects in a subset of sympathetic neurons, primarily in the superior cervical ganglia (SCG), which innervate salivary, parotid, submandibular glands, and nasal mucosa. Phox2B and tyrosine hydroxylase mark sympathetic neurons, and were used to follow SCG during proliferation and migration. They show that a subset of SCG neurons failed to migrate to their final rostral position between vertebral levels C1 and C4. Moreover, SCG neurons were reduced in size and number, which corresponds to an observed increase in cell death. Finally, defects in SCG axon outgrowth and neuronal morphology likely contribute to an observed reduction in innervation of target tissues. Some Prader-Willi patients have difficulty swallowing due to decreased saliva production, suggesting an analogous disruption could be the cause.

Exit the pool (Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool by Nina Solberg, Ondrej Machon, and Stefan Krauss, Dev Dyn237:1799–1811) Canonical Wnt signaling, through β-catenin, is required for hippocampal and dentate gyrus (DG) development. But its precise role in the development of these tissues is not clear. Just before formation of DG progenitor cells, Solberg, Machon, and Krauss, decreased Wnt signaling in mice by driving expression of the inhibitor, Dickkopf1 (Dkk1) in the developing cortex and hippocampus. They found, similar to conditional mutants in Wnt3A and β-catenin, that there was a diminution of the hippocampus and a severe reduction in granule cells of the DG. Furthermore, they determined that reduced cell number in the DG was caused by an increase in cell cycle length and a decrease in proliferation of the progenitor pool. Importantly, adults lack two DG structures, the internal blade and part of the external blade. This finding shows that there was no compensation as development proceeded, suggesting the progenitor pool was depleted during embryogenesis.