A key goal of modern neuroscience involves understanding how connections in the brain form and function. Such a knowledge is essential to better inform how defects in the exquisitely complex steps of nervous system growth underlie neuropsychiatric and neurodevelopmental disorders. In the last 40 years, studies of the nervous system in the fruit fly Drosophila melanogaster enabled the discovery of a wealth of molecular and genetic mechanisms that drive the development of these synaptic connections – specialized cell-to-cell connections that are the essential substrate for information flow and processing in the nervous system. The major driver of knowledge focused on studies at the neuromuscular junction due to its ease of examination. Analogous studies in the central nervous system lagged behind due to a lack of genetic accessibility of specific central neuron classes, appropriate synaptic labels compatible with cell-type specific access, and high resolution, quantitative imaging strategies. However, understanding how synapses in central circuits form remains a prerequisite to understanding brain development. In the last decade, a host of new tools and techniques made possible the extension of genetic studies of synapse organization into central circuits and greatly enhanced our understanding of central synapse formation, organization, and maturation. In this review, we consider the current state-of-the-field, focusing on two major elements. We first discuss the tools, technologies, and strategies developed to visualize and quantify synapses in vivo in genetically identifiable neurons of the Drosophila CNS. Second, we explore in depth how these tools enabled a clearer understanding of synaptic development and organization in different circuits of the fly brain and discovered novel molecular mechanisms that underlie synapse formation. These studies establish multiple brain regions in the fly as powerful in vivo genetic models that offer novel insights into synaptogenic regulators and mechanisms of neural development.

Substantial evidence indicates that bisphenol A (BPA), a ubiquitous environmental chemical used in the synthesis of polycarbonate plastics and epoxy resins, can impair brain development. Clinical and epidemiological studies exploring potential connections between BPA and neurodevelopmental disorders in humans have repeatedly identified correlations between early BPA exposure and developmental disorders, like attention deficit/hyperactivity disorder and autism spectrum disorder. Investigations using invertebrate and vertebrate animal models have revealed that developmental exposure to BPA can impair multiple aspects of neuronal development, including neural stem cell proliferation and differentiation, synapse formation, and synaptic plasticity—neuronal phenotypes that are thought to underpin the fundamental changes in behavior associated neurodevelopmental disorders. Consistent with BPA-associated neuronal phenotypes, behavioral analyses of BPA-treated animals have shown significant impacts on behavioral endophenotypes related to neurodevelopmental disorders, including altered locomotor activity, learning and memory deficits, and anxiety-like behavior. To contextualize the correlations between BPA and neurodevelopmental disorders in humans, this review summarizes current literature reporting on the developmental neurotoxicity of BPA in laboratory animals, with an emphasis on neuronal phenotypes, molecular mechanisms, and behavioral outcomes. The collective works described here predominantly support the notion that gestational exposure to BPA should be regarded as a risk factor for neurodevelopmental disorders.

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to stablish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contacts with additional cells. In this review, we will focus on the role of two important families of cell-cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with especial attention in the cooperative actions among the two families of C-CAMs.