“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.
PCP orientation (The Planar Cell Polarity Pathway in Vertebrate Development by Carolien Wansleeben and Frits Meijlink, Dev Dyn240:616–626) The wealth of information about planar cell polarity (PCP)—the pathway that orients cells within a planar sheet in the same direction—can be enough to make your head spin. This comprehensive, well-organized review should set straight even the most frizzled, er, frazzled, reader. The authors tackle the broad subject by subdividing it into the biological processes in which PCP plays a role, ensuring that the larger significance is always within view. They discuss old favorites, such as how PCP regulates the intricate cell migration patterns in the gastrula, as well as newer findings, like its emerging role in tubule morphogenesis. In each case comparisons are made between vertebrates and Drosophila, where PCP was first discovered and where considerable progress is still being made. The authors also speculate about additional developmental processes, and diseases, in which this widely used pathway may take part.
Refining Wg (Sulfated Is a Negative Feedback Regulator of Wingless in Drosophila by Jia You, Tatyana Belenkaya, and Xinhua Lin, Dev Dyn240:640–648) The family of cell surface molecules, heparan sulfate proteoglycans (HSPGs), modulate signaling and distribution of the morphogen Wingless (Wg). Here, You et al. investigate whether the endosulfatase Sulf1, which removes 6-O sulfates from mature HS chains, also indirectly affects Wg. They find that phenotypes of loss of function sulf1 flies are consistent with the idea that Sulf1 limits Wg activity. What's more, experiments where sulf1 is depleted or overexpressed, suggest that sulf1 exerts its affect by limiting levels of extracellular Wg. Epistasis analysis reveals thatsulf1 modifies just one of two HSPGs previously shown to modulate Wg signaling, the glypican Division abnormally delayed (Dally), but not Dally-like-protein (Dlp). Of interest, Wg is necessary and sufficient to activate sulf1 expression, demonstrating that sulf1 is a feedback regulator of Wg. Combined, the results suggest that sulf1 is another tool with which the embryo fine-tunes Wg, ensuring proper development.
Advancing beyond pluripotency (Negative Autoregulation of Oct3/4 Through Cdx1 Promotes the Onset of Gastrulation by Sharon Zins Rousso, Rachel Ben-Haroush Schyr, Michal Gur, Noam Zouela, Hadas Kot-Leibovich, Yehuda Shabtai, Natalia Koutsi-Urshanski, Danila Baldessari, Graciela Pillemer, Christof Niehrs, and Abraham Fainsod, Dev Dyn240:796–807) Although stem cell biologists fixate on pluripotency, arguably, mechanisms that initiate the transition to germ layer differentiation equally interesting to developmental biologists. With this in mind, Rousso et al. performed an unbiased microarray screen and identified the caudal-type homeobox transcription factor Cdx1 as a repressor of a family of pluripotency maintenance genes, Oct3/4 (Pou5f1), during the onset of Xenopus gastrulation. Consistent with a role in acquisition of differentiation characteristics, Cdx1 morphants display delayed gastrulation and expression of mesendoderm markers, and enhanced proliferation. However, Oct3/4 overexpression and loss of expression experiments reveal that the relationship between Cdx1 and these factors is unexpectedly complex. During late blastula Oct3/4 positively regulates Cdx1, thus using a negative autoregulatory loop to ensure its own demise. This aspect of the pathway is mediated by fibroblast growth factor (FGF); abrogation of the FGF pathway in the presence of overexpressed Oct3/4 results in attenuated Cdx1 expression. During early gastrulation, the negative autoregulatory loop is dismantled, and Oct3/4 switches to repressing Cdx1. At this point, as other work shows, additional pathways such as Wnt and Nodal take over the job of activating Cdx1. Why Oct3/4 switches from its activator role remains unknown and may be key to understanding how the early embryo begins to acquire differentiation characteristics.