Axon targeting in the Drosophila visual system

The neuronal wiring of the Drosophila melanogaster visual system is constructed through an intricate series of cell-cell interactions. Recent studies have identified some of the gene regulatory and cytoskeletal signaling pathways responsible for the layer-specific targeting of Drosophila photoreceptor axons. Target selection decisions of the R1-R6 subset of photoreceptor axons have been found to be influenced by the nuclear factors Brakeless and Runt, and target selection decisions of the R7 subset of axons have been found to require the cell-surface proteins Ptp69d, Lar and N-cadherin. A role for the visual system glia in orienting photoreceptor axon outgrowth and target selection has also been uncovered.     

Microtubule polymerization: one step at a time

The dynamic assembly of microtubules is a key factor in many of their functions in the cell and recent experiments give new insight into this process at the molecular level.     

Cancer genomics: one cell at a time

The study of single cancer cells has transformed from qualitative microscopic images to quantitative genomic datasets. This paradigm shift has been fueled by the development of single-cell sequencing technologies, which provide a powerful new approach to study complex biological processes in human cancers.     

Neuronal networks: dissection one channel at a time

Researchers working on neuronal networks are increasingly taking advantage of the ability to overexpress particular molecular components such as channels. What hope do such studies hold for understanding neuronal phenotype and its role in network function?     

Lateral root initiation: one step at a time

Plant growth relies heavily on a root system that is hidden belowground, which develops post-embryonically through the formation of lateral roots. The de novo formation of lateral root organs requires tightly coordinated asymmetric cell division of a limited number of pericycle cells located at the xylem pole. This typically involves the formation of founder cells, followed by a number of cellular changes until the cells divide and give rise to two unequally sized daughter cells. Over the past few years, our knowledge of the regulatory mechanisms behind lateral root initiation has increased dramatically. Here, I will summarize these recent advances, focusing on the prominent role of auxin and cell cycle activity, and elaborating on the three key steps of pericycle cell priming, founder cell establishment and asymmetric cell division. Taken together, recent findings suggest a tentative model in which successive auxin response modules are crucial for lateral root initiation, and additional factors provide more layers of control.     

Modeling madness in mice: one piece at a time

Mouse models that recapitulate the full phenotypic spectrum of a psychiatric disorder, such as schizophrenia, are impossible. However, a more piecemeal recreation of phenotypic components is feasible and promises to harness the power of animal models using approaches that are either off limits or confounded by drug treatment in humans. In that context, animal models will have a central and indispensable role in the process of discovering the causes of psychiatric disorders and generating novel, mechanism-based treatments. Here, we discuss current approaches used to generate animal models of psychiatric disorders, address the different components of these disorders that can be modeled in animals, and describe currently available analytical tools. We also discuss accumulating empirical data and take an in-depth look at what we believe to be the future of animal models made possible by recent advances in psychiatric genetics.     

Revisiting the central dogma one molecule at a time

The faithful relay and timely expression of genetic information depend on specialized molecular machines, many of which function as nucleic acid translocases. The emergence over the last decade of single-molecule fluorescence detection and manipulation techniques with nm and ? resolution and their application to the study of nucleic acid translocases are painting an increasingly sharp picture of the inner workings of these machines, the dynamics and coordination of their moving parts, their thermodynamic efficiency, and the nature of their transient intermediates. Here we present an overview of the main results arrived at by the application of single-molecule methods to the study of the main machines of the central dogma.     

Spotting the mistakes, one molecule at a time

In this issue of Structure, Cho and colleagues provide intriguing insight into the first steps of the DNA mismatch repair process. By using single-molecule techniques, they show that the protein MutS undergoes two different types of diffusion on error-containing DNA in an ATP-dependent way.     

Saving eyesight,one gene at a time

Kai Yao’s group used prime editing to repair a blindness-causing mutation in the Pde6b gene in the mouse retina. This breakthrough was made possible by a Cas9 nickase that is not constrained by a protospacer adjacent motif (PAM) sequence requirement. This innovation brings prime editing technology one step closer to correcting disease-causing mutations at will.     

Raising grateful children one day at a time

ABSTRACT

We examined micro developmental processes related to the socialization of children's gratitude by testing whether parents who engage in more frequent daily socialization practices targeting children's gratitude reported more frequent gratitude displays by their children after controlling for potential confounds. 101 parent-child dyads completed a baseline lab visit followed by a seven-day diary study. Using multi-level modeling, we found that parents who engaged in more frequent gratitude socialization acts reported more frequent displays of gratitude by their children across the seven-days (between-dyad effect) and that on days when a parent engaged in more socialization acts than usual parents reported relative increases in gratitude displays by their children (within-dyad effect). These findings show that parent socialization acts are associated with children’s displayed gratitude and point to the need for future work to explore reactive and proactive parent-child interactions that may underlie these associations as well as associations between micro-developmental and macro-developmental processes.     

Finishing mitosis, one step at a time

The final stages of mitosis begin in anaphase, when the mitotic spindle segregates the duplicated chromosomes. Mitotic exit is then completed by disassembly of the spindle and packaging of chromosomes into daughter nuclei. The successful completion of mitosis requires that these events occur in a strict order. Two main mechanisms govern progression through late mitosis: dephosphorylation of cyclin-dependent kinase (Cdk) substrates and destruction of the substrates of the anaphase-promoting complex (APC). Here, we discuss the hypothesis that the order of late mitotic events depends, at least in part, on the order in which different Cdk and APC substrates are dephosphorylated or destroyed, respectively.