Highlights in DD


  • Julie Kiefer

“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 more direct hit (Dev Dyn237:403–410). Myotonic Dystrophy (DM) Types 1 and 2 are caused by expansion of microsatellite repeats in two different genes. The DM disease phenotype may be more directly caused by malfunctioning RNA splicing factors, including the three Muscleblind proteins, which are gummed up by microsatellite repeat mRNA. The hypothesis is corroborated by results from this study, which show that mice deficient in Muscleblind2 (Mbnl2) display key DM features, including myotonia and skeletal myopathy. Possibly accounting for the myotonia phenotype, the authors also demonstrate that the mice exhibit aberrant splicing of a chloride channel, Clcn1, an event implicated in human myotonic dystrophy. They further demonstrate that CLCN1 protein expression is absent from some muscle regions. The results suggest that DM symptoms can be attributed to multiple causes, including deficiency of Mbnl2 and Mbnl1, both incompletely recapitulating the disease. Studying the disease models separately will allow researchers to investigate individual pathways that contribute to DM.

Oct-3/4's double life (Dev Dyn237:464–475) The POU transcription factor Oct-3/4 is most celebrated as the master regulator of totipotency in ES and germ cells. But how can researchers claim to understand the molecule when its role beyond implantation is mostly undocumented? Working like a private eye, Downs fastidiously tracked Oct-3/4's embryonic whereabouts in the mouse gastrula, uncovering evidence that the gene leads a double life. As it turns out, Oct-3/4 gene expression lurks in several epiblast-derived cell types, implicating it in regulating development of several tissues, among them definitive endoderm and the umbilical vasculature. Most surprising was her discovery that the gene is expressed in cells previously shown to be developmentally restricted by potency mapping. By the eight-somite stage, Oct-3/4 gene expression all but disappears, save for expression in primordial germ cells and cell clusters in the allantois. With its cover blown, Oct-3/4 can't hide for long. It is only a matter of time before Oct-3/4's postimplantation intentions are exposed.

Breaking up is hard to do (Dev Dyn237:565–579) “pucker,” “zippering,” “cleavage.” These words aren't excerpted from a romance novel, but are from a tale describing Xenopus blastomere cleavage furrow closure. The egg is effectively divided in two by the addition of new membrane along the cleavage plane, which expands opposing basolateral domains of the embryo's superficial epithelia. Shortly after their separation, the new surfaces “reunite” and adhere to one another. Using time-lapse microscopy, Danilchik and Brown for the first time carefully document the role of protrusions in this process. They find that dynamic protrusions operate at two locations during early and late steps of furrow closure. They appear at apical–basolateral margins during the first half of compaction, mediate local purse-string constrictions independent of the contractile ring, and function to enable blastomere contact. When basolateral domains stop expanding, a second set of protrusions spans the furrow, instigating blastomere adhesion. Their findings may have implications toward mechanisms that regulate similar processes, such as epithelial sheet closure during wound repair. It seems that the best part of breaking up is getting back together.