“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 will spotlight 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.
A Taste of the Future (Dev Dyn237:2378–2393) What do feather buds, hair follicles, and taste bud papillae have in common? Epidermal growth factor (EGF) signaling helps pattern all of these structures. Previously, it was known that EGF was involved in patterning of skin structures, but EGF receptor (EGFR) knockout mice had such severe facial deformities that a definitive role in patterning papillae could not be determined. By using a tongue culturing system, Liu et al. now show that EGF signaling inhibits formation of fungiform papillae—located in the anterior part of the tongue. Developing tongues dissected from embryos and grown in culture had a significant decrease in the number of papillae when exposed to exogenous EGF and an increase when exposed to EGFR inhibitors. While both EGF and EGFR are initially expressed in papillae and inter-papillae epithelium, EGFR becomes increasingly restricted to inter-papillae just before papillae development. Furthermore, addition of EGF to cultured tongues increased the number of dividing cells in this region. These data argue that EGF signaling inhibits papillae formation by expanding the inter-papillae space. The authors augment their findings by showing that combinatorial action of Akt, MEK/ERK, and p38 MAPK mediate the EGF signaling. Future experiments using the tongue culturing system should help identify additional factors involved in papillae development.
Bound Together (Dev Dyn237:2963–2972) Nkx3.1 is a homeodomain containing transcription factor that is required for prostate development and is considered a putative tumor suppressor—most prostate precancerous cells and carcinomas are missing one copy of the gene. To gain a better understanding of how Nkx3.1 functions, Wang et al. looked for interacting proteins using a yeast two hybrid system. The authors found multiple proteins that bind to human Nkx3.1 including Fem1b, which is chiefly known for the role of its Caenorhabditis elegans homolog in male development. Further experiments showed that mouse Fem1b is expressed in prostate cells overlapping with Nkx3.1. Moreover, Fem1b knockout mice have a reduction in ductal tip number in the anterior prostate lobe and a reduction in secretory protein synthesis—similar to phenotypes found in Nkx3.1 mutants. Multiple functions have been suggested for Fem1b, but it was recently shown to be a component of an E3 ubiquitin ligase complex. One possibility is that Nkx3.1 is a target of this complex. Despite this open question, we now know that Nkx3.1 and Fem1b are bound and together impact prostate development. We look forward to learning how.
Illumenating Vascular Spheroids (Dev Dyn237:2918–2925) By culturing vascular spheroids that contain a lumen and respond to physiological signals, Gentile et al. have generated vascular micro-tissue that could eventually be used to help engineer blood vessels. Embryonic mouse allantoic tissue was cultured using a hanging droplet method. This same method had previously been shown to successfully produce spheroids containing an outer layer of smooth muscle cells, and an inner layer of endothelial cells expressing vascular markers. However, luminal-like dark spaces in the interior of the spheroid were small and dispersed. When the authors incubated the cultures with VEGF they were able to create spheroids that contained the two cell layers, but also a large contiguous lumen. Injection of quantum dot nanocrystals into the spheroid showed that the space was similar to a vessel lumen in that the Qdots were retained. Furthermore, exposure of these lumenated spheroids to the vascular contraction signal, KCl, caused a reduction in diameter while subsequent treatment with vasorelaxants, such as acetylcholine, caused an increase in diameter. These more representative spheroids hold promise for engineering vessels as well as for illuminating some of the mysteries of vascular development.