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Proper functioning of the nervous system relies not only on the generation of a vast repertoire of distinct neural cell types but also on the precise neural circuitry within them. How the generation of highly diverse neural populations is regulated during development remains a topic of interest. Landmark studies in Drosophila have identified the genetic and temporal cues regulating neural diversity and thus have provided valuable insights into our understanding of temporal patterning of the central nervous system. The development of the Drosophila central complex, which is mostly derived from type II neural stem cell (NSC) lineages, showcases how a small pool of NSCs can give rise to vast and distinct progeny. Similar to the human outer subventricular zone (OSVZ) neural progenitors, type II NSCs generate intermediate neural progenitors (INPs) to expand and diversify lineages that populate higher brain centers. Each type II NSC has a distinct spatial identity and timely regulated expression of many transcription factors and mRNA binding proteins. Additionally, INPs derived from them show differential expression of genes depending on their birth order. Together type II NSCs and INPs display a combinatorial temporal patterning that expands neural diversity of the central brain lineages. We cover advances in current understanding of type II NSC temporal patterning and discuss similarities and differences in temporal patterning mechanisms of various NSCs with a focus on how cell-intrinsic and extrinsic hormonal cues regulate temporal transitions in NSCs during larval development. Cell extrinsic ligands activate conserved signaling pathways and extrinsic hormonal cues act as a temporal switch that regulate temporal progression of the NSCs. We conclude by elaborating on how a progenitor's temporal code regulates the fate specification and identity of distinct neural types. At the end, we also discuss open questions in linking developmental cues to neural identity, circuits, and underlying behaviors in the adult fly. [ABSTRACT FROM AUTHOR]

The nervous system consists of a vast diversity of neurons and glia that are accurately assembled into functional circuits. What are the mechanisms that generate these diverse cell types? During development, an epithelial sheet with neurogenic potential is initially regionalised into spatially restricted domains of gene expression. From this, pools of neural stem cells (NSCs) with distinct molecular profiles and the potential to generate different neuron types, are specified. These NSCs then divide asymmetrically to self-renew and generate post-mitotic neurons or glia. As NSCs age, they experience transitions in gene expression, which further allows them to generate different neurons or glia over time. Versions of this general template of spatial and temporal patterning operate during the development of different parts of different nervous systems. Here, I cover our current knowledge of Drosophila brain and optic lobe development as well as the development of the vertebrate cortex and spinal cord within the framework of this above template. I highlight where our knowledge is lacking, where mechanisms beyond these might operate, and how the emergence of new technologies might help address unanswered questions. [ABSTRACT FROM AUTHOR]

Neurons originate from neural stem cells and then synapse with stereotyped partners to form neuronal circuits. Recent findings indicate that several molecular mechanisms generating neuronal identity can rewire neuronal connectivity in the Drosophila brain when genetically manipulated. In this review, I discuss how mechanisms generating neuronal identity could activate molecular pathways essential for circuit formation and function. Next, I propose that the central complex of Drosophila, an ancient and highly conserved brain region essential for locomotor control and navigation, is an excellent model system to further explore mechanisms linking circuit development to circuit function.

Neurons originate from neural stem cells and then synapse with stereotyped partners to form neuronal circuits. Recent findings indicate that several molecular mechanisms generating neuronal identity can rewire neuronal connectivity in the Drosophila brain when genetically manipulated. In this review, I discuss how mechanisms generating neuronal identity could activate molecular pathways essential for circuit formation and function. Next, I propose that the central complex of Drosophila , an ancient and highly conserved brain region essential for locomotor control and navigation, is an excellent model system to further explore mechanisms linking circuit development to circuit function. [ABSTRACT FROM AUTHOR]

The Drosophila visual system has become a premier model for probing how neural diversity is generated during development. Recent work has provided deeper insight into the elaborate mechanisms that control the range of types and numbers of neurons produced, which neurons survive, and how they interact. These processes drive visual function and influence behavioral preferences. Other studies are beginning to provide insight into how neuronal diversity evolved in insects by adding new cell types and modifying neural circuits. Some of the most powerful comparisons have been those made to the Drosophila visual system, where a deeper understanding of molecular mechanisms allows for the generation of hypotheses about the evolution of neural anatomy and function. The evolution of new neural types contributes additional complexity to the brain and poses intriguing questions about how new neurons interact with existing circuitry. We explore how such individual changes in a variety of species might play a role over evolutionary timescales. Lessons learned from the fly visual system apply to other neural systems, including the fly central brain, where decisions are made and memories are stored. [ABSTRACT FROM AUTHOR]

A small pool of neural progenitors generates the vast diversity of cell types in the CNS. Spatial patterning specifies progenitor identity, followed by temporal patterning within progenitor lineages to expand neural diversity. Recent work has shown that in Drosophila, all neural progenitors (neuroblasts) sequentially express temporal transcription factors (TTFs) that generate molecular and cellular diversity. Embryonic neuroblasts use a lineage-intrinsic cascade of five TTFs that switch nearly every neuroblast cell division; larval optic lobe neuroblasts also use a rapid cascade of five TTFs, but the factors are completely different. In contrast, larval central brain neuroblasts undergo a major molecular transition midway through larval life, and this transition is regulated by a lineage-extrinsic cue (ecdysone hormone signaling). Overall, every neuroblast lineage uses a TTF cascade to generate diversity, illustrating the widespread importance of temporal patterning. [ABSTRACT FROM AUTHOR]

Transposition of mobile genetic elements can radically alter genome structure and sequence. In doing so, they can alter gene expression and cellular function. Perhaps unsurprisingly, this potentially catastrophic process is heavily constrained, especially in the germ line where aberrations lead to sterility or could be passed onto the next generation. However, recent studies in mammals and fruit flies suggest that transposition happens at measurable levels in the brain, and possibly more so in some cell types than in others. This has led to the suggestion that certain cell types may utilize transposable elements to diversify cellular properties. In this review, we discuss these findings and ideas in light of our current understanding of transposons and their control in the fly, and the growing evidence for an involvement of transposition in neurological disease in humans. [ABSTRACT FROM AUTHOR]

Detecting the temporal relationship among events in the environment is a fundamental goal of the brain. Following pulses of rhythmic stimuli, neurons of the retina and cortex produce activity that closely approximates the timing of an omitted pulse. This omitted stimulus response (OSR) is generally interpreted as a transient response to rhythmic input and is thought to form a basis of short-term perceptual memories. Despite its ubiquity across species and experimental protocols, the mechanisms underlying OSRs remain poorly understood. In particular, the highly transient nature of OSRs, typically limited to a single cycle after stimulation, cannot be explained by a simple mechanism that would remain locked to the frequency of stimulation. Here, we describe a set of realistic simulations that capture OSRs over a range of stimulation frequencies matching experimental work. The model does not require an explicit mechanism for learning temporal sequences. Instead, it relies on spike timing-dependent plasticity (STDP), a form of synaptic modification that is sensitive to the timing of pre- and post-synaptic action potentials. In the model, the transient nature of OSRs is attributed to the heterogeneous nature of neural properties and connections, creating intricate forms of activity that are continuously changing over time. Combined with STDP, neural heterogeneity enabled OSRs to complex rhythmic patterns as well as OSRs following a delay period. These results link the response of neurons to rhythmic patterns with the capacity of heterogeneous circuits to produce transient and highly flexible forms of neural activity. [ABSTRACT FROM AUTHOR]

Objective: The olfactory system depends on the proper gene expression of olfactory receptor (OR) genes in olfactory receptor neurons (ORN) and the proper transfer of olfactory signals to the brain. ORNs have to make two important choices. They have to choose to express one gene from the large repertoire of OR genes and send their axons to a special destination in the brain. Our studies focus on the elucidation of the role of the Iroquois complex (IroC) family, a family of transcription factor genes consisting of three conserved genes called araucan (ara), caupolican (caup) and mirror (mirr) in the differentiation of odorant receptor neurons. Methods: To elucidate the function of the IroC genes, we tried to generate mutants for all three genes using the CRISPR/Cas technology. In addition, to examine localization of each gene we aimed to add fluorescence proteins to each gene locus using the CRISPR/Cas. The obtained mutants were examined using RNASequencing to identify differentially expressed genes. The identified genes were confirmed by qRT-PCR. Verification by in situ hybridization is underway. Furthermore, the effects of iroC genes on the differentiation of cells are followed by the lineage- tracing experiments. Results: In this study we showed that the IroC genes are expressed in ORNs. While the maxillary palp iroC is expressed in the pb2 subset of the ORNs, expression in the adult antenna appears to be more dispersed. In order to identify the iroC target genes, we first used RNASeq analysis using triple mutant fly antennae and maxillary palps and identified the differentially expressed genes. We show that 11 OR genes and 23 transcription factors are differentially expressed. qRT-PCR experiments confirmed that expression of the OR genes is decreased. Conclusion: Our results confirm that iroC genes play a role in OR gene regulation. However, further experiments will show if this regulation is direct or indirect. [ABSTRACT FROM AUTHOR]

The Drosophila visual system integrates input from 800 ommatidia and extracts different features in stereotypically connected optic ganglia. The development of the Drosophila visual system is controlled by gene regulatory networks that control the number of precursor cells, generate neuronal diversity by integrating spatial and temporal information, coordinate the timing of retinal and optic lobe cell differentiation, and determine distinct synaptic targets of each cell type. In this chapter, we describe the known gene regulatory networks involved in the development of the different parts of the visual system and explore general components in these gene networks. Finally, we discuss the advantages of the fly visual system as a model for gene regulatory network discovery in the era of single-cell transcriptomics., (© 2020 Elsevier Inc. All rights reserved.)

Transposition of mobile genetic elements can radically alter genome structure and sequence. In doing so, they can alter gene expression and cellular function. Perhaps unsurprisingly, this potentially catastrophic process is heavily constrained, especially in the germ line where aberrations lead to sterility or could be passed onto the next generation. However, recent studies in mammals and fruit flies suggest that transposition happens at measurable levels in the brain, and possibly more so in some cell types than in others. This has led to the suggestion that certain cell types may utilize transposable elements to diversify cellular properties. In this review, we discuss these findings and ideas in light of our current understanding of transposons and their control in the fly, and the growing evidence for an involvement of transposition in neurological disease in humans., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Despite investigations dating back to the 19(th) century, the functional role of different cell types in the brain remains largely unknown. Using realistic computer simulations, we have recently shown that neural diversity can generate patterns of complex activity that were traditionally interpreted as irreducible noise. Such complex activity may directly contribute to both cognitive and behavioral outcomes, including motor control, perception and memory.