“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.
A palatable explanation (Hoxa2 Plays a Direct Role in Murine Palate Development by Tara M. Smith, Xia Wang, Wei Zhang, William Kulyk, and Adil J. Nazarali, Dev Dyn238:2364–2373) It was a perplexing finding. Hoxa2−/− mice have cleft secondary palates—a structure that divides nasal and oral cavities. Yet is not detected in the first branchial arch—the precursor to palatal shelves. Were observed cleft palates secondary to a mispositioned tongue, whose precursors do express Hoxa2? Smith etal. were on the case. Their first clue, they and others found that Hoxa2−/− tongues appear to be positioned correctly. Second, Hoxa2 is expressed in the developing palate during stages when palate shelves emerge, elevate, and fuse. Third, Hoxa2−/− mice exhibit enhanced cell proliferation and elevated expression of genes that regulate palate mesenchymal cell proliferation. Fourth, Hoxa2−/− palates cultured in the absence of tongue failed to fuse even though excised medial palate shelves placed in juxtaposition had the ability to fuse. The evidence suggests that excess mesenchymal cell proliferation in Hoxa2−/− palates interrupts contact between palate shelves, thus preventing their fusion. In short, cleft palates appear to be a primary defect in Hoxa2−/− mice. Case closed.
MyoX gaining traction (Myosin-X Is Required for Cranial Neural Crest Cell Migration in Xenopus laevis by Yoo-Seok Hwang, Ting Luo, Yanhua Xu, and Thomas D. Sargent, Dev Dyn238:2522–2529) The journey from cranial neural crest (CNC) precursor to its terminal derivatives, including jaw cartilage and cranial ganglia, is an arduous one. Cells must travel long distances and negotiate local extracellular signaling cues before they can differentiate. Here, Hwang etal. tease out how MyoX, an unconventional myosin enriched in CNC, helps these cells reach their final state. When zygotic MyoX is knocked down by morpholino injection, CNC induction remains unaffected, but migration is slowed and cells fail to terminally differentiate. Transplantation of MyoX knockdown cells into a control host reveals that the phenotypes are cell autonomous, and not the result of a defective inductive signaling by adjacent tissues. In vitro, MyoX knockdown cells plated on fibronectin-coated slides failed to migrate or extend filopodia, and attached only weakly. Together, the work supports a primary role for MyoX in migration and substrate adhesion. The authors speculate that differentiation defects stem from cells not being in the right place at the right time, and/or failure to receive substrate-dependent inductive cues. Without good traction, CNCs cannot make the home stretch.
Easy “enucleation” (Enucleation of Feeder Cells and Egg Cells With Psoralens by Thomas J. McGarry, Michael Bonaguidi, Ljuba Lyass, John A. Kessler, Jason M. Bodily, and Lynn Doglio, Dev Dyn238:2614–2621) Enucleated feeder cells, surrogate mothers of the Petri dish, nurture the growth of other cells but do not divide themselves. Essential as these cells are, methods of enucleation remain cumbersome (manual), expensive (gamma-irradiation), or toxic (Mitomycin C). McGarry etal. present a simpler method to enucleate cells: treatment with psoralens and ultraviolet (UV) light. The technique introduces extensive cross-linking between the two DNA strands that prevents DNA replication. The authors show that psoralen-enucleated feeder cells successfully sustain the growth of human embryonic stem cells for nearly a week. Easily adaptable to accommodate an automated system, this method may breathe life into high throughput creation of feeder cells. Psoralen treatment is also at least 90% efficient at enucleating Xenopus eggs for use in nuclear transplantation studies. Although psoralen+UV-treated mouse eggs could be fertilized, the embryos arrested around the two-cell stage because of checkpoint activation. Thank the mother of invention, necessity, for giving birth to a rapid, inexpensive, and nontoxic alternative for generating feeder cells and enucleating the eggs of organisms with delayed cell cycle checkpoint activation, such as Xenopus or Drosophila.