Highlights in DD
2009; Wiley; Volume: 238; Issue: 10 Linguagem: Inglês
10.1002/dvdy.22061
ISSN1097-0177
Autores Resumo“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. There and back again (Beyond Early Development: Xenopus as an Emerging Model for the Study of Regenerative Mechanisms by Caroline W. Beck, Juan Carlos Izpisúa Belmonte, and Bea Christen, Dev Dyn 238:1226–1248) In J.R.R. Tolkien's The Hobbit, Bilbo Baggins taps into idle internal resources to accomplish a seemingly insurmountable task, after which he transforms back into his former, homely self. Likewise, the otherwise ordinary Xenopus tail, limb, and lens acquire the remarkable ability to regenerate, but for only a short while. The transient nature of this feat makes it a particularly intriguing case study. What elixir of molecules endows these tissues with this remarkable ability? Why does the capability to regenerate vanish over time? By following multiple facets of Xenopus regeneration from morphological to gene expression changes, and recent functional studies, this review presents tools to address these and other questions. A particularly noteworthy feature of this article is the set of text boxes highlighting puzzling or controversial topics (i.e., “Does the tail regenerate by means of a blastema or regeneration bud?”). The review demonstrates that Xenopus will be a steadfast ally for scientists wishing to fulfill an important quest: to discover how the power to regenerate is acquired, and to activate that magical quality in other settings. Everything in moderation (CDK9/Cyclin Complexes Modulate Endoderm Induction by Direct Interaction With Mix.3/mixer by Haiqing Zhu, Joanne R. Doherty, Emin Kuliyev, and Paul E. Mead, Dev Dyn 238:1346–1357) Work too hard and you lose your friends, work too little and you lose your job. Improper balance of the homeodomain transcription factor Mix.3/mixer also has its consequences. Too much induces excess endoderm, and too little creates excess mesoderm at the expense of endoderm. In pursuit of protein partners that keep Mix.3 activity in moderation dosage, the authors performed a yeast two-hybrid screen and identified cyclin-dependent kinase 9 (CDK9). They find that while Mix.3 mRNA injected into one-cell Xenopus activates a luciferase reporter bearing Mix.3 binding sites, co-injection of CDK9 and cyclin T2, which complexes with the kinase, inhibits this activation by 5-fold. To understand requirements of a functional Mix.3 modulation complex, Mix.3 was replaced with Mix.3▵123, a mutant that lacks the CDK9 binding domain, and in another experiment, CDK9 with a kinase-dead version. In both cases, reporter activation resembled that from injection of Mix.3 alone, showing that Mix.3 modulation requires direct binding to active CDK9. Furthermore, unlike a cyclin T2 complex, a cyclin K complex failed to attenuate Mix.3 reporter activation, demonstrating that not all cyclins are created equal. Validating in vitro work, the findings were re-iterated in in vivo animal cap assays and in whole embryos with endodermal marker expression as readout. The authors also found that CDK9/cyclin T2 complex modulates repressor activity of Mix.3 in vitro, but not in vivo, the latter possibly the consequence of the complex's affects on other parts of the Xbra pathway. The work elucidates ways in which the embryo keeps from having too much, or too little, of a good thing. Making the mark (Database of Queryable Gene Expression Patterns for Xenopus by Michael J. Gilchrist, Mikkel B. Christensen, Odile Bronchain, Frédéric Brunet, Albert Chesneau, Ursula Fenger, Timothy J. Geach, Holly V. Ironfield, Ferdinand Kaya, Sadia Kricha, Robert Lea, Karine Massé, Isabelle Néant, Elodie Paillard, Karine Parain, Muriel Perron, Ludivine Sinzelle, Jacob Souopgui, Raphaëll Thuret, Qods Ymlahi-Ouazzani, and Nicolas Pollet, Dev Dyn 238:1379–1388). Without an efficient way to wade through thousands of experimentally revealed gene expression patterns, they are merely beauty marks: pleasing to the eye but of limited usefulness. To facilitate the hunt for specific patterns, Gilchrist and colleagues used a novel combination of manual and computational annotation methods to create a queryable expression pattern database of Xenopus genes: XenMARK (http://informatics.gurdon.cam.ac.uk/apps/XenMARK/). Annotators add expression patterns to the database by “coloring in” blank, stage-specific, computerized templates of Xenopus embryos. Manual annotation allows for transposition of expression patterns from embryos that are rotated or distorted with respect to the template, more precise staging, and other judgment calls. To expedite database set-up and encourage users to add their own experimental data, annotation is easy, rapid, and can be completed without extensive anatomical knowledge. Following data input, XenMARK translates pattern information into x–y coordinates, making them searchable. A highly useful feature of the database search engine is that, in addition to searching by sequence or keyword, the user can also color in a template to define their own expression pattern to search by, click on a region of the embryo to see all intersecting expression patterns, or look for patterns similar to that of an in situ image that is already annotated in the database. Soon image x–y coordinates will be automatically translated to anatomical ontology terms, enabling anatomy-based searches. More than a collection of pretty pictures, XenMARK sets a new standard for elucidating colocalized gene expression.
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