“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.
Remodeling tools (Dev Dyn236:671–683) For a good remodel, just the right tools are needed to disassemble the old to make room for the new. During cardiac remodeling, myocardium of the outflow tract (OFT) is lost and replaced with smooth muscle before becoming arterial tissue. C.B. Kern et al., set out to determine how the job is done. Here, they show that versican, an extracellular matrix chondroitin sulfate proteoglycan is a multifunctional tool in the OFT. Adenoviral-mediated expression of an uncleavable form of versican in vivo and in vitro shows that the intact protein promotes cell–cell association, stabilizing the myocardial layer. Just before remodeling, myocardial versican is proteolytically cleaved to generate a fragment, DPEAAE. Ectopic expression of a DPEAAE-like fragment augments detachment of myocardial cells from the myocardial layer, facilitating formation of the mature OFT. These results suggest that versican fortifies OFT walls, and its DPEAAE proteolytic fragment functions to break the walls down, clearing the way for their smooth muscle replacement.
Addressing the Numb conundrum (Dev Dyn236:696–705) The so-called “Numb conundrum” is based on seemingly contradictory results from mouse Numb mutants. Some observed phenotypes support the widely held belief that Numb antagonizes Notch's role in maintaining neural progenitors, while others substantiate the opposite conclusions. This study reveals that the key to solving this puzzle may lie in understanding how Numb mutants affect the four Numb isoforms. Numb1 and 3 contain an insertion in their proline-rich region and are predominantly expressed early in development, whereas numb2 and 4 are mainly expressed postnatally and into adulthood. Consistent with expression data, numb1 and 3 suppress differentiation of primary neural progenitors and p19 cells, whereas numb2 and 4 enhance differentiation. Despite differing biological roles, all isoforms inhibit Notch in vitro, illustrating that they likely also modulate other signaling pathways.
Cell assassin (Dev Dyn236:1025–1035) Looking to kill some cells? Pick your poison, perhaps diphtheria toxin? Maybe brute force is more your style—how about laser ablation? You say you want a genetic approach to temporarily remove certain cell populations for regeneration studies? Luckily, there is a new method that is just for you. First, you need transgenic fish with the Escherichia coli enzyme Nitroreductase (NTR) under a tissue specific promoter. Next, quietly slip Metronidazole (Mtz) in the fish water. In the presence of NADH or NADPH, NTR reduces Mtz, making it a DNA cross-linking agent. This cytotoxic drug effectively triggers cell death in both proliferating and quiescent cells. Wash away the Mtz, and not only is the killing spree over, but any incriminating evidence is gone.