Proper wiring of the nervous system is crucial for behavior, and defects in nervous system connectivity have been associated with cognitive impairment and neurological disease. How do neurons acquire their diverse morphologies, and how do they interact during development to form the intricate "maps" and circuits of the nervous system? While neural circuit assembly requires the intricate choreography of diverse processes, the specific placement of axons and dendrites is particularly important in determining how circuits process information. Using two well-characterized model circuits in Drosophila and mouse, I will discuss the genetic and molecular mechanisms that regulate how axons find their targets, and how dendrites adopt specific morphologies. The Drosophila olfactory system is an excellent model of wiring specificity, with stereotyped 1:1 connectivity between 50 classes of peripheral olfactory receptor neurons (ORNs) and 50 classes of central projection neurons (PNs). While studying how this connectivity pattern emerges during development, I discovered that a family of guidance factors called semaphorins regulates axon and dendrite development through multiple mechanisms. Specifically, secreted Semaphorin-2b acts both cell-autonomously and non-autonomously to specify developing axon trajectory. Indeed, secreted semaphorins mediate both axon-axon interactions and axon-target interactions. Furthermore, Sema-2b is negatively regulated by the Notch pathway during ORN development, and thus inextricably links cell fate determination to axon trajectory choice. Developmental trajectory defects have devastating consequences for the final targeting of ORN axons. Together, these findings reveal how reiterative use of the same molecules can seamlessly pattern neural circuits during successive developmental stages, and highlight novel mechanisms of semaphorin signaling. To study dendrite morphogenesis, I turned to the mouse cerebellum, another well-characterized neural circuit. This project arose as part of a larger effort to explore how neurotrophins regulate central brain development. Neurotrophins are well known for their roles in regulating the survival, differentiation, and plasticity of central and peripheral neurons. However, their functions in neural circuit assembly remain mysterious. Using a sparse mosaic genetic technique, I discovered that the neurotrophin receptor TrkC is specifically required for cerebellar Purkinje cell dendrite arborization. TrkC mutant Purkinje cells exhibited stunted dendritic trees with decreased complexity and length. Interestingly, removing TrkC from all Purkinje cells did not cause dendrite defects, raising the possibility of a competitive mechanism. Indeed, a series of conditional knockout and virus-based experiments suggest that TrkC and its ligand NT-3 drive competitive interactions between Purkinje cells. As functionally important NT-3 comes from the presynaptic partners of Purkinje cells, such "dendritic competition" contrasts with the classic target-derived "neurotrophic hypothesis." Together, these studies highlight the usefulness of mosaic genetic approaches in revealing the cellular mechanisms of neural circuit assembly. They also uncover surprising new roles for two historic signaling systems, and demonstrate how cells integrate both cell-intrinsic and environmental cues to establish the exquisite architecture of the nervous system.

This book offers representative examples from fly and mouse models to illustrate the ongoing success of the synergistic, state-of-the-art strategy, focusing on the ways it enhances our understanding of sensory processing. The authors focus on sensory systems (vision, olfaction), which are particularly powerful models for probing the development, connectivity, and function of neural circuits, to answer this question: How do individual nerve cells functionally cooperate to guide behavioral responses? Two genetically tractable species, mice and flies, together significantly further our understanding of these processes. Current efforts focus on integrating knowledge gained from three interrelated fields of research: (1) understanding how the fates of different cell types are specified during development, (2) revealing the synaptic connections between identified cell types (“connectomics”) using high-resolution three-dimensional circuit anatomy, and (3) causal testing of how iden tified circuit elements contribute to visual perception and behavior.

This book has brought together leading investigators who work in the new arena of brain connectomics. This includes ‘macro-connectome’ efforts to comprehensively chart long-distance pathways and functional networks; ‘micro-connectome’ efforts to identify every neuron, axon, dendrite, synapse, and glial process within restricted brain regions; and ‘meso-connectome’ efforts to systematically map both local and long-distance connections using anatomical tracers. This book highlights cutting-edge methods that can accelerate progress in elucidating static ‘hard-wired’ circuits of the brain as well as dynamic interactions that are vital for brain function. The power of connectomic approaches in characterizing abnormal circuits in the many brain disorders that afflict humankind is considered. Experts in computational neuroscience and network theory provide perspectives needed for synthesizing across different scales in space and time. Altogether, this book provides an integrated view of the challenges and opportunities in deciphering brain circuits in health and disease.

For a thorough study of the dynamics of particular brain compounds it is now possible to use and combine various molecular neuroanatomical methods (e.g. in situ hybridization, receptor localisation and immunocytochemistry) in a quantitative way on whole brain sections maintaining morphological details. Molecular Neuroanatomy deals with the many practical aspects and recent developments in these areas. The theoretical background of many techniques is presented, as well as clear, step-by-step instructions on the preparation and application of all the methods and techniques described in this book. It will be invaluable to all those working in the field of neuroscience. Available in both hardback and paperback, with colour illustrations.

1 Kevin Moses It is now 25 years since the study of the development of the compound eye in Drosophila really began with a classic paper (Ready et al. 1976). In 1864, August Weismann published a monograph on the development of Diptera and included some beautiful drawings of the developing imaginal discs (Weismann 1864). One of these is the first description of the third instar eye disc in which Weismann drew a vertical line separating a posterior domain that included a regular pattern of clustered cells from an anterior domain without such a pattern. Weismann suggested that these clusters were the precursors of the adult ommatidia and that the line marks the anterior edge of the eye. In his first suggestion he was absolutely correct - in his second he was wrong. The vertical line shown was not the anterior edge of the eye, but the anterior edge of a moving wave of patterning and cell type specification that 112 years later (1976) Ready, Hansen and Benzer would name the "morphogenetic furrow". While it is too late to hear from August Weismann, it is a particular pleasure to be able to include a chapter in this Volume from the first author of that 1976 paper: Don Ready! These past 25 years have seen an astonishing explosion in the study of the fly eye (see Fig.