The elegant and precise experiments of Nicole Le Douarin in the 70s on the influence of position on the outcome of transplanted neural crest cells (Le Douarin et al., 1975), and the culture experiments by Storey Landis and Paul Patterson on the factors that influence a cell to express noradrenergic or cholinergic neurotransmitters (Wolinsky et al., 1985) set the stage for thinking that the identity of a cell was in many ways scripted but malleable. Case studies draw from research on face recognition, language, executive function, representations of objects, number and theory of mind. We will undoubtedly see more surprising instances in which molecular factors function opposite to their canonical role. This approach showed, for example, that cortical interneurons come from a fountainhead in subcortical (ganglionic eminence) regions, migrate long distances to the cortex, and can be grouped by transcription factor expression and physiological responses (Butt et al., 2005). This covers a lot of ground, ranging from factors influencing prenatal development to those that provoke deterioration associated with old age. While most of its subject matter has been known and studied by the medical community for decades, the field did not emerge as an independent pursuit until recently. What genes regulate the cytoskeleton and dendritic process outgrowth to yield such different forms? Refinement of exuberant axonal connections by elimination of collaterals was also demonstrated in the CNS (Cowan et al., 1984). This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Are these oddities, or just the first examples? I. So much has transpired in unraveling events, many counterintuitive, during development. Using this technique in combination with x-irradiation to block division, many laboratories, notably Joseph Altman's, charted neurogenesis in almost every region in the rodent brain. We must ask how the many factors that are expressed at the same time and place might act in concert, then use the new experimental approaches to deduce function. And just as this work emerged around the mid-90s, genetic analysis revealed that UNC-6 was a conserved molecule with the same function in worm commissural neurons (Culotti, 1994; Serafini et al., 1994). What is there that we look forward to? In the late 90s Doetsch and Alvarez-Buylla found that there are stem cells in the adult brain that have glial properties (Doetsch et al., 1999). This covers a lot of ground, ranging from factors influencing prenatal development to those that provoke deterioration associated with old age. Prospective doctoral candidates often have some flexibility in choosing their degree path, since it is a product of both neuroscience and biology. Forty years ago we would have never dreamed of these possibilities! These tools also paved the way for studies of neurogenesis, cell lineage, and axon guidance in the simple nervous system of the insect (Goodman et al., 1984). A recent surprise was that a low-density lipoprotein receptor, Lrp4, has been found to be the long-sought receptor for agrin (Kim et al., 2008). These marvelously evocative accounts told the story of how the cellular components of a brain region are elaborated, and even made inferences about mechanisms. Although we now think of cell specification as a new subject driven by the knowledge of genes that direct cell fate, forty years ago, many experiments examined the role of the environment in determining cell identity. These remain the canonical foursome of guidance effects, and growth cones likely rely on all four mechanisms (Tessier-Lavigne and Goodman, 1996). What followed thereafter was a virtual explosion of work that characterized more guidance factor families and receptors—the Slits and Robo receptors, Semaphorins and neuropilin and plexin receptors, and the receptor tyrosine kinase Ephs and ephrins, identified through genetic analysis in flies and worms, by good detective work in higher organisms, and by matching expression of orphan receptors to scenarios in vivo, respectively (Huber et al., 2003). These studies of neurogenesis and neuronal fate were accompanied in the late 90s by studies on naturally occurring mouse mutants or ones in which the genes that were discovered to cause human cortical malformations were knocked out, such as doublecortin, mutated in human X-linked lissencephaly (Gleeson et al., 1999). What Can I Do with a Master’s Degree in Psychology? And the notion of “use it or lose it” based on Hebb's hypothesis was extended to the idea that winning a competition with inputs that fired less frequently was enabled by uptake of growth factors from the target. A growing list of factors are proposed to dampen the state of structural plasticity, including local inhibitory synapses and later-developing interneurons (Morishita and Hensch, 2008), Nogo, an oligodendrocyte-derived myelin protein that inhibits regenerating axons (McGee et al., 2005), PirB, a major histocompatability complex 1 receptor that interacts with the Nogo receptor (Syken et al., 2006), and chondroitin sulfate proteoglycans (Pizzorusso et al., 2006). How do we go forth? Journals and funding agencies need to better appreciate the inherent value in “descriptive” cellular anatomy and to support these much-needed investigations, performed so gloriously by too few (Morgan et al., 2005; Lu et al., 2009). Once molecular tools became available, methods were developed to perturb the molecules and read the consequences, to deduce function. In recent years, we have focused on individual subroutines—one part of a trajectory or a small set of molecules. Forty years ago in the emerging field of developmental neurobiology, neuroanatomists studied cellular development in their favorite brain region by annotating static Golgi preparations at different time points. Thirty years later, we know many factors that designate where and when a synapse should form, in a give-and-take involving agrin signaling from the nerve to MuSK, part of the agrin receptor, rapsyn as an effector, and the dystrophin-glycoprotein complex and its cytoplasmic component, α dystrobrevin, to modulate maturation and maintenance of the postsynaptic apparatus (Sanes et al., 2001). After bulk labeling axons with HRP and studying their morphology, synaptic relationships could then be studied by examining details of axons arbors in the light microscope followed by ultrastructural analysis (Mason, 1982b). My guess is yes. Undoubtedly the biggest boon to developmental studies was the discovery in the late 80s of tracers that could be precisely applied in minute quantities to fixed tissue. Many of these guidance families may work in concert, such as when slit receptors silence netrin receptors to allow commissural axons to exit the spinal cord midline (Stein and Tessier-Lavigne, 2001) or when IgCAMs collaborate with Semaphorin receptors to enable commissural growth in the forebrain (Bechara et al., 2007). Cell biologists examined how growth cones grow in tissue culture, probed how cells survived, and discovered nerve growth factor with clever embryological, culture, and biochemical methods, and tested the concept of specificity—that neurons connected to their targets through chemical affinities—highlighted by Sperry's studies (Sperry, 1963) on the regenerating frog visual system. Developmental neuroscience and genetics probably are Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. Down the road, we can expect these approaches to delineate afferent-target interactions during development, and to measure activity changes during different phases of development. Neuroscience is the study of how the nervous system develops, its structure, and what it does. Nevertheless, it came as a surprise that slices and even whole embryos of rodent brain could be cultured and used to reveal many principles in all phases of development (Polleux and Ghosh, 2002). movement, developmental theories have typically been referred to as stage, phase, life course theories, and, more recently, developmental science (Damon & Lerner, 2006). The decade of the developing brain, TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation, Synapse elimination in the central nervous system, Collapse of growth cone structure on contact with specific neurites in culture, Surface and cytoskeletal markers of rostrocaudal position in the mammalian nervous system, Green fluorescent latex microspheres: a new retrograde tracer, Synaptic activity and the construction of cortical circuits, Lrp4 is a receptor for Agrin and forms a complex with MuSK, Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells, Diversity of ganglion cells in the mouse retina: unsupervised morphological classification and its limits, The glial nature of embryonic and adult neural stem cells, The generation of neuromuscular specificity, Cholinergic differentiation of presumptive adrenergic neuroblasts in interspecific chimeras after heterotopic transplantations, Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision, The determination of projection neuron identity in the developing cerebral cortex, Cell-to-substratum adhesion and guidance of axonal elongation, Ocular dominance columns and their development in layer IV of the cat's visual cortex: a quantitative study, Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors, GPR56 regulates pial basement membrane integrity and cortical lamination, Function and regulation of local axonal translation, Anatomical traces of juvenile learning in the auditory system of adult barn owls, Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system, A role for local calcium signaling in rapid synaptic partner selection by dendritic filopodia, Asymmetric modulation of cytosolic cAMP activity induces growth cone turning, Axon retraction and degeneration in development and disease, Specification of motor axon trajectory by ephrin-B:EphB signaling: symmetrical control of axonal patterning in the developing limb, Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis, Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs, Rapid formation and remodeling of postsynaptic densities in developing dendrites, Development of terminal arbors of retinogeniculate axons in the kitten. A highlight from such studies was to see that upon cell division, proteins are distributed asymmetrically, and this determines cell polarity and/or cell fate (Doe, 1996). Developmental Neuroscience It describes the cellular and molecular mechanisms by which complex nervous systems emerge during embryonic development and throughout life. We now believe that these gene codes specify cell fate: for example, whether a neural precursor becomes an interneuron or a motor neuron (Jessell, 2000), or becomes a retinal ganglion cell instead of an amacrine cell (Li et al., 2004). Modern developmental neuroscientists find themselves a part of a complex and growing profession that has numerous applications for both humans and animals. We will hear of more instances in which the same molecule is used for quite different aspects of development. For example, FGFs regulate transcription factors that mediate graded guidance factor expression in the midbrain and optic tectum, and they also modulate the tempo of radial glial cell differentiation to neuronal progenitors particularly in rostral cortex (Chen et al., 2009; Regan et al., 2009). Work on the neuromuscular junction, autonomic ganglia, climbing fibers, and visual pathways (LGN, tectum, and cortex) fortified the concept of competition between axons with different activity patterns, in adjusting their terminations in the target. Confocal and multiphoton microscopy now allow us to see fine details well below the surface of fixed tissue as well as in living preparations, and to reconstruct and rotate stacks of images in three dimensions. Hubel and Wiesel's enormous contribution to understanding how early experience affected visual behavior (Wiesel and Huber, 1965) set the stage for the now avidly studied topic of activity-dependent sculpting of wiring; but they could not address questions at the mechanistic level. There are also some job opportunities for those with undergraduate or graduate degrees. In the mid-90s, another shift in our view took place: unique combinations of transcription factors are expressed in different cell classes over the course of development. In addition to Sperry's notion of chemical labels for synapse specificity, another potent undercurrent that has fueled developmental studies of late stemmed from Hubel and Wiesel's work in the 50s through the late 70s (Daw, 2009) that the pattern and extent of sensory experience early in life molds connectivity. Using transgenic technology on the whole animal or gene delivery by viruses or electroporation, a gene of interest can be added back to rescue a deletion phenotype or can be expressed prematurely or in an ectopic location. Now, at the Annual Meeting we have an overwhelming sense of ignorance in trying to glean the newest information from the hundreds of posters in the Development section each morning and afternoon, flickering sound bites about expression of a new gene or manipulation of another gene. Researchers have several options when it comes to employment, including private companies, universities and medical institutions. Developmental neuroscience is often a research area at many universities offering a Ph.D. We block function with antibodies or dominant/negative forms. In one of the Society's first short courses, “New approaches in Developmental Neurobiology” in 1981, four of the 11 lectures were devoted to the production of monoclonal antibodies. Now we can enumerate the genes that define a coordinate system that produces, for example, the dorsoventral axis of the spinal cord (Jessell, 2000), diversification of motor neuron columns (Dasen and Jessell, 2009), and the laminar structure, foliation, and molecular organization of the cerebellum (Sillitoe and Joyner, 2007). Sauer and others in the 30s outlined the steps in cell division in the neural tube, and showed that the nucleus moved from the pia to the ventricular zone, where it divided, then moved outward again to repeat the cycle (Sauer, 1935). Histogenetic studies charted the development of dendrites, and found that some cells, like the Purkinje cell, initially form a “koosh ball” of short processes, then withdraw those and put out thicker branched trees. Corey Goodman argued further that it was possible to use such simple systems to follow neurogenesis and axonal pathfinding in identified cells (Goodman et al., 1984). And finally, we should apply our computational power to understand the orchestration of cellular processes and signals that sculpt the emerging brain. They deduced cellular interactions and dependency from mutants in which cells were missing or had defective migration and cell–cell relationships (Rakic and Sidman, 1973). Such experiments showed that in the limb, afferents establish connections with their proper target even if the anterior–posterior axis was rotated. evolutionary psychology), developmental neuroscience, and genetics. Departments of Pathology and Cell Biology, Neuroscience, and Ophthalmology, Columbia University, College of Physicians and Surgeons, 630 W. 168th Street, New York, NY 10032. According to the Society for Neuroscience (SfN) the three main objectives of neuroscience are to 1. Adult neurogenesis occurs in the subventricular zone (SVZ) of the mammalian brain, from which neurons migrate to the olfactory bulb, and in the subgranular zone (SGZ) of the hippocampal formation. In addition, one can learn from articles recounting the trends of the previous decades (Reichardt, 1985; Cowan, 1998), a commentary on specificity (Easter et al., 1985), and a most engaging one published at the millennium (Jessell and Sanes, 2000). Because of the enormity of the subject, we chose to cite select reviews, commentaries, and references, and apologize for any omissions. Neuroscience is the study of how the human nervous system develops and functions. The development of the nervous system, or neural development, or neurodevelopment, refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. 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