Highlights in DD

Abstract

“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. Dissecting Down syndrome models (Embryonic and Not Maternal Trisomy Causes Developmental Attenuation in the Ts65Dn Mouse Model for Down Syndrome by Joshua D. Blazek, Cherie N. Billingsley, Abby Newbauer, and Randall J. Roper, Dev Dyn 239:1645–1653) Proper data interpretation is dependent upon a thorough understanding of experimental tools. The most widely used model for Down syndrome, or trisomy 21, is the Ts65Dn mouse. In an effort to determine the etiology of DS phenotypes, the authors discover that Ts65Dn embryos have attenuated development and are smaller than control embryos. The authors show that developmental attenuation is a consequence of embryonic trisomy. However, they find that another phenotype, a smaller than expected ratio of trisomic offspring at birth that further decreases at weaning stages, is influenced by the maternal genetic background. At embryonic stages, the small ratio is a product of maternal trisomy—Ts65Dn offspring are bred from Ts65Dn mothers. While at postnatal day 10, the decreased ratio may be due to a commonly found Pde6brd/rd maternal background mutation, which causes blindness in Ts65Dn mothers and possibly renders them less able to care for their young. The analysis highlights the importance of understanding the possible contributions of the maternal genetic background of the disease model during the analysis of embryonic and early postnatal phenotypes. Future studies will benefit from careful consideration of all underlying genetic contributions to phenotypes associated with disease models and diseased humans. Initial invasion (Cellular Dynamics of Epithelial Clefting During Branching Morphogenesis of the Mouse Submandibular Gland by Yuichi Kadoya and Shohei Yamashina, Dev Dyn 239:1739–1747) The mouse submandibular gland (SMG), a model for epithelial branching, starts out resembling a cauliflower with floret-like terminal clusters that are connected to an epithelial stalk. Over two days, the bulky primordia blossoms into a mature, many branched, tree-like organ. Epithelial branching starts with a cleft that dives into and carves apart terminal clusters. Here, Kadoya and Yamashima use live imaging of SMG cultures impregnated with a non-cell permeable fluorescent tracer, and transmission electron microscopy (TEM), and to identify characteristics of cleft formation. Clefts initially form when a narrow fissure extends between epithelial cells, but clefts are dynamic in that some retract, and the distal, invading end often changes direction before settling on a path of invasion. The latter finding suggests that cleft elongation must occur in the presence of epithelial cells with certain, unknown attributes. When a cleft invades between cells, the distal tip seemingly drives right into a cell making a small groove. At one side of the groove, this cell makes up the cleft sidewall, and at the other side the cell extends a small cytoplasmic projection that the authors call a shelf. Because the shelf harbors anchoring filaments, the authors suggest it might form an attachment to the basement membrane that covers the distal tip, generating a mechanical force that drives cleft extension. These careful observations call into question previous models of cleft elongation, and carve a path for future studies. Finding common ground (Molecular Haeckel by Richard P. Elinson and Lorren Kezmoh, Dev Dyn 239:1905–1918) In 1870, the German biologist and philosopher, Ernst Haeckel, authored a textbook that included his depiction of a 10-somite embryo with a caption that read, “embryo of a mammal or bird”. Although the inaccuracy of this and other similar figures outraged his fellow anatomists, in some ways, Haeckel was ahead of his time. In the 1980s, the field of evolutionary developmental biology (evo-devo) was born, based on the premise that diverse species share conserved gene regulatory networks that are tweaked throughout evolution to create morphological diversity. Incorporating concepts from evo-devo, Elinson and Kezmoh have updated Haeckel's concept of the “generic vertebrate embryo.” The authors conducted a thorough survey of the literature to identify regulatory genes whose expression in a specific tissue or organ was conserved across major vertebrate model systems. The information was transformed into pictoral form, where the names of the genes themselves are made into art and used to create the organs and tissues of a generic vertebrate embryo. The result is a set of drawings that are eye-catching, instructive, and most importantly, they are accurate. These are the first generation of so-called Molecular Haeckels; future versions could include additional criteria such as gene function.