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The bristle sensillum of the imago of Drosophila is made of four cells that arise from a sensory organ precursor cell (SOP). This SOP is selected within proneural clusters (PNC) through a mechanism that involves Notch signalling. PNCs are defined through the expression domains of the proneural genes, whose activities enables cells to become SOPs. They encode tissue specific bHLH proteins that form functional heterodimers with the bHLH protein Daughterless (Da). In the prevailing lateral inhibition model for SOP selection, a transcriptional feedback loop that involves the Notch pathway amplifies small differences of proneural activity between cells of the PNC. As a result only one or two cells accumulate sufficient proneural activity to adopt the SOP fate. Most of the experiments that sustained the prevailing lateral inhibition model were performed a decade ago. We here re-examined the selection process using recently available reagents. Our data suggest a different picture of SOP selection. They indicate that a band-like region of proneural activity exists. In this proneural band the activity of the Notch pathway is required in combination with Emc to define the PNCs. We found a sub-group in the PNCs from which a pre-selected SOP arises. Our data indicate that most imaginal disc cells are able to adopt a proneural state from which they can progress to become SOPs. They further show that bristle formation can occur in the absence of the proneural genes if the function of emc is abolished. These results suggest that the tissue specific proneural proteins of Drosophila have a similar function as in the vertebrates, which is to determine the time of emergence and position of the SOP and to stabilise the proneural state.

All vertebrates can produce new neurons postnatally in discrete regions of their nervous system, but only some lower vertebrates (fish and amphibians) can significantly repair several neural structures, including brain, spinal cord, retina, olfactory and auditory-vestibular system, to compensate for neural tissue loss and recover significant functionality. Some regenerative ability, however, is found also in reptiles and birds, and even in mammals. The recognition that neurogenesis indeed occurs in the CNS of all adult vertebrates challenges the view that there is a simple relationship between maintenance of neurogenic regions in the adult CNS and regenerative capability. The aim of this review is to revisit this relationship in the light of recent literature focusing on selected examples of neurogenesis and regeneration, and discuss possible frameworks that may help to elucidate the relationship between adult neurogenesis and regeneration. This could provide useful paradigms for harnessing regeneration in the human CNS., (© 2011 The Author. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

mKirre is a novel member of the immunoglobulin superfamily, which is abundant in the developing and adult brain. In the present study, we showed mKirre gene expression in mouse sensory organs during development using in situ hybridization and immunohistochemistry. At embryonic day (E) 11.5, E15.5, and E17.5, we first detected signals for mKirre mRNA in the developing cochleae, retinae, and olfactory neuroepithelia, respectively. After birth, strong signals were observed in these sensory organs. In addition, at this stage, we found its expression in trigeminal ganglion neurons and neuronal populations forming sensory pathways in the olfactory bulb, midbrain, and pons. Furthermore, double-immunofluorescence staining revealed that nephrin-immunoreactivity was overlapping to mKirre-expressing cells in the developing sensory organs. These results suggest that mKirre may be involved in the establishment of the pathway from sensory organs to the brain not only in a homophilic manner but also with its heterophilic interaction to nephrin.

The pattern of the external sensory organs (SO) in Drosophila depends on the activity of the basic helix-loop-helix (bHLH) transcriptional activators Achaete/Scute (Ac/Sc) that are expressed in clusters of cells (pro-neural clusters) and provide the cells with the potential to develop a neural fate. In the mesothorax, the GATA1 transcription factor Pannier (Pnr), together with its cofactor Chip, activates ac/sc genes directly through binding to the dorso-central enhancer (DC) of ac/sc. We identify the LIM-homeo domain (LIM-HD) transcription factor Islet (Isl) by genetic screening and investigate its role in the thoracic pre-patterning. We show that isl loss-of-function mutations result in expanded Ac expression in DC and scutellar (SC) pro-neural clusters and formation of ectopic sensory organs. Overexpression of Isl decreases pro-neural expression and suppresses bristle development. Moreover, Isl is coexpressed with Pnr in the posterior region of the mesothorax. In the DC pro-neural cluster, Isl antagonizes Pnr activity both by dimerization with the DNA-binding domain of Pnr and via competitive inhibition of the Chip-bHLH interaction. We propose that sensory organ pre-patterning relies on the antagonistic activity of individual Chip-binding factors. The differential affinities of these binding-factors and their precise stoichiometry are crucial in specifying pre-patterns within the different pro-neural clusters.

Sexual dimorphism in the nervous system is required for sexual behavior and reproduction in many metazoan species. However, little is known of how sex determination pathways impose sex specificity on nervous system development. In C. elegans, the conserved sexual regulator MAB-3 controls several aspects of male development, including formation of V rays, male-specific sense organs required for mating. Here we show that MAB-3 promotes expression of the proneural protein LIN-32 in V ray precursors by transcriptional repression of ref-1, a member of the Hes family of neurogenic factors. Mutations in ref-1 restore lin-32::gfp expression and normal V ray development to mab-3 mutants, suggesting that ref-1 is the primary target of MAB-3 in the V ray lineage. Proteins related to MAB-3 (DM domain proteins) control sexual differentiation in diverse metazoans. We therefore suggest that regulation of Hes genes by DM domain proteins may be a general mechanism for specifying sex-specific neurons.

What is the nature of the genetic programme that allows neurons to extend their axons and connect to other neurons with a high degree of specificity? Work on the sensory neurons of the fly has shown how the control of neuronal identity is embedded in the general developmental programme of the organism. The ongoing analysis of pathfinding mutants suggests plausible mechanisms for the translation of neuronal identity into axonal behaviour.

This report examines the development of the dopaminergic system in the primary antennosensory centres (antennal lobes) of the brain of the honey bee, Apis mellifera, and the effects of dopamine on neurite outgrowth of antennal-lobe neurons in vitro. Antibodies raised against dopamine were used to follow the development of a small population of dopamine-immunoreactive neurons that invade the antennal lobes during metamorphic adult development. Immunopositive somata associated with the antennal lobes were first detected at stage 2 of the nine stages of metamorphic adult development, but processes of these neurons within the antennal-lobe neuropil did not exhibit immunostaining until pupal stage 3. Severe depletion of primary sensory input to the right antennal lobe early in metamorphic adult development or removal of the right antenna from newly emerged bees did not alter the expression of dopamine immunoreactivity in the antennal-lobe neuropil. The presence of dopamine in developing antennal lobes was confirmed by using high performance liquid chromatography with electrochemical detection. Levels of dopamine were significantly higher at pupal stage 4 than at all other stages examined. This surge in dopamine levels coincided with rapid growth and compartmentalisation of the antennal-lobe neuropil. Exogenously applied dopamine (50 microM) enhanced the growth of antennal-lobe neurons in vitro, but only in cells derived from pupae at stage 5 of metamorphic adult development. The early appearance of dopamine-immunoreactive neurons and the effects of dopamine on stage 5 antennal-lobe neurons in vitro support the view that dopamine plays a role in the developing brain of the honey bee., (Copyright 1999 Wiley-Liss, Inc.)

The bristle mechanosensory organs of the adult fly are composed of four different cells that originate from a single precursor cell, pI, via two rounds of asymmetric cell division. Here, we have examined the pattern of cell divisions in this lineage by time-lapse confocal microscopy using GFP imaging and by immunostaining analysis. pI divided within the plane of the epithelium and along the anteroposterior axis to give rise to an anterior cell, pIIb, and a posterior cell, pIIa. pIIb divided prior to pIIa to generate a small subepithelial cell and a larger daughter cell, named pIIIb. This unequal division, oriented perpendicularly to the epithelium plane, has not been described previously. pIIa divided after pIIb, within the plane of the epithelium and along the AP axis, to produce a posterior socket cell and an anterior shaft cell. Then pIIIb divided perpendicularly to the epithelium plane to generate a basal neurone and an apical sheath cell. The small subepithelial pIIb daughter cell was identified as a sense organ glial cell: it expressed glial cell missing, a selector gene for the glial fate and migrated away from the sensory cluster along extending axons. We propose that mechanosensory organ glial cells, the origin of which was until now unknown, are generated by the asymmetric division of pIIb cells. Both Numb and Prospero segregated specifically into the basal glial and neuronal cells during the pIIb and pIIIb divisions, respectively. This revised description of the sense organ lineage provides the basis for future studies on how polarity and fate are regulated in asymmetrically dividing cells.

To learn about the acquisition of neural fate by ectodermal cells, we have analyzed a very early sign of neural commitment in Drosophila, namely the specific accumulation of achaete-scute complex (AS-C) proneural proteins in the cell that becomes a sensory organ mother cell (SMC). We have characterized an AS-C enhancer that directs expression specifically in SMCs. This enhancer promotes Scute protein accumulation in these cells, an event essential for sensory organ development in the absence of other AS-C genes. Interspecific sequence comparisons and site-directed mutagenesis show the presence of several conserved motifs necessary for enhancer action, some of them binding sites for proneural proteins. These and other data indicate that the enhancer mediates scute self-stimulation, although only in the presence of additional activating factors, which most likely interact with conserved motifs reminiscent of NF-kappaB-binding sites. Cells neighboring the SMC do not acquire the neural fate because the Notch signaling pathway effectors, the Enhancer of split bHLH proteins, block this proneural gene self-stimulatory loop, possibly by antagonizing the action on the enhancer of the NF-kappaB-like factors or the proneural proteins. These data suggest a mechanism for SMC committment.

Taste sensilla of flies are composed of only a few cells, all of which have different functions. Depending on the species and on the sensillum type, there are from 2-5 neurons, each of which has its own stimulus specificity, and each of which makes a different contribution to the fly's behavior. In addition, taste sensilla include several nonneuronal cells that are important both for the development of the sensillum and for its functioning. The component cells of a sensillum derive from a single epidermal precursor according to a stereotyped sequence of mitoses. This review focuses on the different phenotypes of the component cells of taste sensilla, particularly the stimulus sensitivity and central neuronal anatomy of the receptor neurons, and on the development of this multicellular organ from a single precursor cell.

Sex-pheromone components released by Manduca sexta females are detected solely by male-specific olfactory receptor neurons that innervate long sensilla trichodea on the male antennae. To facilitate studies of the development and physiology of these receptor cells, we have produced primary in vitro cultures of cells dissociated from pupal male antennae. These cultures comprise several morphological types of cells, 2 of which have been characterized immunocytochemically with a pair of monoclonal antibodies that were shown previously to recognize certain antigens in olfactory receptor neurons at defined stages of development. The good correlation between in vivo and in vitro expression of these antigens suggests that the immunocytochemically recognized cells are olfactory receptor neurons that follow at least partially their normal course of differentiation in vitro.