Highlights in DD

Abstract

“Highlights” is a new feature that 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. Quieting the Noise (Dev Dyn 236:1416–1421) Without a conductor, musicians drift out of synch, their song fragmenting into a disorganized clatter of notes. Similarly, adjacent cells in the posterior presomitic mesoderm (PSM) rely on oscillators to coordinate the rhythmic cycling of segmentation gene transcription, translation, and transcriptional repression. One challenge the segmentation clock faces is that 10–15% of PSM cells are in M-phase, during which time transcription and translation are quiescent, meaning initiation of their segmentation cycles are staggered. In this review, the authors propose a model for how synchrony is achieved. PSM cells have an intracellular oscillator led by hairy, which in a direct autoinhibitory feedback loop represses its own expression, and also represses Delta expression. Delta, in turn, is an intercellular oscillator that binds the Notch receptor on adjacent cells, and activates hairy expression. In vivo and mathematical modeling experiments support their model that Delta reduces biological noise by coupling oscillator cycling in neighboring cells. Profiling Endoderm (Dev Dyn 236:1633–1649) If you research molecular mechanisms of endoderm development, then this paper is a must-see. Endoderm, which gives rise to lung, stomach, esophagus, pancreas, liver, duodenum, gallbladder, and intestine, is arguably the least studied of the three primary germ layers. In search of genes that regulate development of these organs, Han and colleagues performed microarray analysis on Xenopus endoderm at three crucial stages: the onset of regional specification, organogenesis, and differentiation of organ-specific cell types. Anterior and posterior endoderm were compared at each stage to enrich for organspecific genes. Their painstaking approach yielded 915 candidates that are differentially expressed by at least threefold. Of these, 104 were selected for in situ hybridization. A table detailing gene expression in individual organs reveals some intriguing patterns. Interested in the liver? You may want to investigate transcription factors Tbx2 and MafB. Curious about the lung? Look into signaling molecules Semaphorin6D and Frizzled-7. The information is there for the taking. Recipe for Mature Chondrocytes (Dev Dyn 236:1954–1962) Science is a lot like cooking. Mix the ingredients, incubate, and voila! Your product is ready. Presented here is a recipe for making mature chondrocytes. The transcription factor Runx2 drives the chondrocyte maturation step, chondrocyte hypertrophy, and regulates osteoblast development. Surprisingly, retroviral overexpression of Runx2 in presomitic mesoderm (PSM) explants fails to activate expression of the chondrocyte hypertrophic marker Collagen X. However, if PSM explants are first treated with Shh then BMP4, signals surrounding developing axial chondrocytes in vivo, then ectopic Runx2 can activate chondrocyte hypertrophy markers. Forced expression of Sox9 or Nkx3.2, transcription factors expressed in immature chondrocytes, can substitute for Shh. In other conditions, Runx2 overexpressing explants instead activate osteopontin, an osteoblast marker, suggesting that Runx2 only activates Collagen X when in the right cellular milieu. In agreement, overexpression of Runx2 in combination with a transcription factor that transduces bone morphogenetic protein signals, Smad1, activates a Collagen X reporter in hypertrophic chondrocytes, but not in fibroblasts or immature chondrocyte primary cultures. What is the permissive factor necessary for chondrocyte maturation? Now that contexts in which it functions are known, it will not be long until the secret ingredient is revealed.