Focus Issue: Time Passages

The development of life remains one of the most fascinating topics in modern biology. Our quest to discover unifying principles is rooted in a desire to find reason and order in processes that are at once overwhelming and chaotic. We have been vigorously engaged in dissecting development across species at molecular and genomic levels. The intricate machineries that have been uncovered so far operate together in precise manners, at not only the right places, but equally important, at the correct times. This week, Science 's Special Issue on Developmental Timing describes our knowledge of some of the rules and measures of time, a core dimension in understanding how development is controlled. Among the most intriguing developmental timepieces are circadian clocks, mechanisms in the central nervous system and in peripheral tissues that respond to light-dark cycles of the environment by exerting corresponding rhythmic control over development. A review in Science by Schultz and Kay compares and contrasts circadian clock regulation of plant and animal developmental programs. STKE Connections Maps by Van Gelder describe the molecular differences but functional similarities between the circadian clocks of mammals and flies. A Review by Pando and Sassone-Corsi on communication between central and peripheral clocks can also be found in the STKE Archives. STKE also presents a Perspective by Goldman on how seasonal photoperiod changes sensed by a mammalian mother can be transmitted to a developing fetus by melatonin, a neuroendocrine hormone whose secretion is rhythmically controlled. Because a fetus lacks a melatonin rhythm of its own, this transmission of information may aid a newborn's initial sense of time and season. For more details on melatonin receptor signaling, see the Perspective by Masana and Dubocovich in the STKE Archives. Another clock appears to control the progressive formation of part of the vertebrate anterior-posterior body axis. Pourquie describes in a Science Review how an oscillator called the segmentation clock governs the rise of embryonic segments from mesodermal cells called "somites" by temporally regulating the signaling molecules Wnt, Notch, and fibroblast growth factor. Asymmetric signaling during mesodermal differentiation is the topic of the Review in the STKE Archives by Whitman and Mercola. How regulated endocytosis of Notch contributes to cell fate specification of sensory cells by controlling the timing of the Notch signal is the subject of the Perspective by Shen and Temple in the STKE Archives. The Perspective in the STKE Archives by Martinez-Arias describes how the timing of the Wnt signal controls Drosophila wing development. The various developmental roles of Wnt are also covered extensively in the Connections Maps database, with Pathways in Drosophila , Xenopus , and Caenhorhabditis elegans . The organization of genes may correspond to their sequential expression in what Kmita and Duboule describe in a Science review as colinearity. Genes encoding the Hox family of transcription factors are clustered and, as such, perhaps represent a prototype for patterning clocks that generate the appropriate spatial and temporal distribution of transcription factors. In the STKE Protocols Archive, a light-based technique that allows for temporal control of gene expression in single cells in developing Drosophila , Xenopus , and zebrafish embryos is described by Minden et al . We are learning that precision in gene silencing is as critical as in inducing gene expression, and a Science review by Carrington and Ambros explains that these are early days in terms of understanding how small RNAs (micro and short-interfering) control developmental timing by interfering with messenger RNAs (mRNAs). This observation has been the basis for the use of RNA interference as a technique to knock down gene expression and determine gene function. An STKE Perspective by Michelson describes how the recent application of RNA interference (RNAi) in a high-throughput screen of the Drosophila genome has uncovered some overlap between the Wingless and Hedgehog signaling pathways, both of which contribute to embryonic development. Other applications of RNAi can be found in the STKE Archive and include two Protocols: Worby et al ., which describes how to perform RNAi in Drosophila cultured cells, and Lassus et al ., which describes how to confirm the specificity of an RNAi effect. Timing of flowering and leaf initiation is covered in Poethig's review in Science , and genetic analysis of plants has identified many genes that mediate the effects of photoperiod, temperature (the thermal clock), and hormones on these events. A Perspective in the STKE Archives by Federoff explains how the plant hormone abscisic acid regulates bud and seed dormancy, growth, and leaf senescence. An STKE Connections Map by Sheen describe the details of cytokinin signaling that regulates plant growth. Timing is important even in the adult, where multipotent cells continue to proliferate and differentiate on cue. Acuto describes how the timing of accurate cell-cell encounters in the immune system is crucial to host survival in the face of pathogen infection. Recent imaging analyses have shown that T cells move more rapidly in living tissue than previously thought, such that a single antigen-presenting dendritic cell can be surveyed by up to 500 T cells in an hour. T cell interaction with the appropriate antigen-bearing dendritic cell stimulates T cell receptor (TCR) activation, survival, and subsequent clonal expansion. Thus, the timing of T cell-dendritic cell encounters regulates T cell development; the precise duration and intensity of TCR activation needed to yield these T cell responses, however, remain unclear. Our current molecular understanding of T cell signaling can be found in an STKE Connections Map by Singer and Koretzky. Time itself will bring the answer to these questions and to many others concerning the role of temporal sequence in development, during maturity, and in the aging organism. Featured in this Focus Issue Perspectives Virtual Journal Related Resources at STKE Connections Maps Reviews Perspectives Protocols Virtual Journal Signal Transduction on the Web