The Drosophila embryo provides a useful model system to study the mechanisms that lead to pattern and cell diversity in the central nervous system (CNS). The Drosophila CNS, which encompasses the brain and the ventral nerve cord, develops from a bilaterally symmetrical neuroectoderm, which gives rise to neural stem cells, called neuroblasts. The structure of the embryonic ventral nerve cord is relatively simple, consisting of a sequence of repeated segmental units (neuromeres), and the mechanisms controlling the formation and specification of (...) the neuroblasts that form these neuromeres are quite well understood. Owing to the much higher complexity and hidden segmental organization of the brain, our understanding of its development is still rudimentary. Recent investigations on the expression and function of proneural genes, segmentation genes, dorsoventral‐patterning genes and a number of other genes have provided new insight into the principles of neuroblast formation and patterning during embryonic development of the fly brain. Comparisons with the same processes in the trunk help us to understand what makes the brain different from the ventral nerve cord. Several parallels in early brain patterning between the fly and the vertebrate systems have become evident. BioEssays 26:739–751, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Insect neurogenesis has been subjected to extensive study and as a result is regarded as being well understood. It is, therefore, all the more surprising when a fundamentally novel aspects of the process is uncovered. Until recently it was thought that the production of central neurons ceased before the emergence of the adult. Recently, however, Cayre et al. have shown that neurogenesis also occurs in the adult brain. Their studies also show that the rate at which adult neuroblasts divide is (...) controlled by hormones, suggesting that hormones may play a more important role in regulating neurogenesis than previously suspected. (shrink)

The relatively simple central nervous system (CNS) of the Drosophila embryo provides a useful model system for investigating the mechanisms that generate and pattern complex nervous systems. Central to the generation of different types of neurons by precursor neuroblasts is the initial specification of neuroblast identity and the Drosophila segment polarity genes, genes that specify regions within a segment or repeating unit of the Drosophila embryo, have emerged recently as significant players in this process. During neurogenesis the segment polarity (...) genes are expressed in the neuroectodermal cells from which neuroblasts delaminate and they continue to be expressed in neuroblasts and their progeny. Loss-of-function mutations in these genes lead to a failure in the formation of neuroblasts and/or specification of neuroblast identity. Results from several recent studies suggest that regulatory interactions between segment polarity genes during neurogenesis lead to an increase in the number of neuroblasts and specification of different identities to neuroblasts within a population of cells. BioEssays 21:472–485, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts arise from the ectoderm (...) in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

The specification of specific and often unique fates to individual cells as a function of their position within a developing organism is a fundamental process during the development of multicellular organisms. The development of the Drosophila embryonic central nervous system serves as an excellent model system in which to clarify the developmental mechanisms that link pattern formation to cell-type specification. The Drosophila embryonic central nervous system develops from a set of neural stem cells termed neuroblasts. Neuroblasts arise from the ectoderm (...) in an invariant pattern, and each neuroblast acquires a unique fate based on its position within this pattern. Two groups of genes recently have been demonstrated to govern the individual fate specification of neuroblasts. One group, the segment polarity genes, enables neuroblasts that develop in different anteroposterior positions to acquire different fates. The second group, referred to as the columnar genes, ensures that neuroblasts that develop in different dorsoventral domains assume different fates. When integrated, the activities of the segment polarity and columnar genes create a Cartesian coordinate system that bestows unique fates to individual neuroblasts as a function of their position of formation within the ectoderm. BioEssays 1999;21:922–931. © 1999 John Wiley & Sons, Inc. (shrink)

Balancing self‐renewal and differentiation of stem cells is an important issue in stem cell and cancer biology. Recently, the Drosophila neuroblast (NB), neural stem cell has emerged as an excellent model for stem cell self‐renewal and tumorigenesis. It is of great interest to understand how defects in the asymmetric division of neural stem cells lead to tumor formation. Here, we review recent advances in asymmetric division and the self‐renewal control of Drosophila NBs. We summarize molecular mechanisms of asymmetric cell (...) division and discuss how the defects in asymmetric division lead to tumor formation. Gain‐of‐function or loss‐of‐function of various proteins in the asymmetric machinery can drive NB overgrowth and tumor formation. These proteins control either the asymmetric protein localization or mitotic spindle orientation of NBs. We also discuss other mechanisms of brain tumor suppression that are beyond the control of asymmetric division. (shrink)

The role of acetylcholinesterase (AChE) in neurotransmission is well known. But long before synapses are formed in vertebrates, AChE is expressed in young postmitotic neuroblasts that are about to extend the first long tracts. AChE histochemistry can thus be used to map primary steps of brain differentiation. Preceding an possibly inducing AChE in avian brains, the closely related butyrylcholinesterase (BChE) spatially fore-shadows AChE-positive cell areas and the course of their axons. In particular, before spinal motor axons grow, their corresponding rostral (...) sclerotomes and myotomes express BChE, and both their neuronal source and myotomal target cells express AChE. Since axon growth has been found inhibited by acetylcholine, it is postulated that both cholinetsreases can attract neurite growth cones by neutralizing the inhibitor. Thus, the early expression of both cholinesterases that is at least partially independent from classical cholinergic synaptogenesis, sheds new light on the developmental and medical significance of these enzymes. (shrink)

Drosophila neural progenitor cells, or neuroblasts, alter their transcriptional profile over time to produce different neural cell types. A recent paper by Pearson and Doe shows that older neuroblasts can be reprogrammed to behave like young neuroblasts, and to produce early neural cell types, simply by expressing the transcription factor, Hunchback.1 The authors show that competence to respond to Hunchback diminishes over time. Mani pulating neural progenitors in this way may have important implications for therapeutic uses of neural stem cells. (...) BioEssays 26:711–714, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Large numbers of cells with unique neuronal specificity are generated during development of the central nervous system of animals. Here we discuss the events that generate cell diversity during early development of the ventral nerve cord of different arthropod groups. Neural precursors are generated in a spatial array in the epithelium of each hemisegment over a period of time. Spatial cues within the epithelium are thought to evolve as embryogenesis proceeds. This spatiotemporal information might generate diversity among the neural precursors (...) in all arthropod groups, although the mechanisms regulating the positioning of individual precursors have diverged. However, distinct strategies for the generation of neuronal diversity have evolved in the different arthropod lineages that appear to correlate with specific modes of ontogenesis. We hypothesize that an evolutionary trend towards reduced cell numbers and possibly rapid embryogenesis in insects has culminated in the appearance of stereotyped neuroblast lineages. BioEssays 27:874–883, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The development of each of the four Malpighian tubules of Drosophila during embryogenesis requires a special cell, the tip cell, to achieve full growth. A central question concerns how the tip cell acquires its unique properties within the tubule primordium. In a recent report(1), a sequence of key gene expression events in both the tip cell and its cellular neighbours is described. The results show that there are some significant parallels between tip cell selection and the mechanisms that help select (...) neuroblasts within the developing neuroectoderm. Beyond these similarities between neural development and tip cell selection, the later differentiation of the tip cell shows some intriguing elements of neural cell differentiation. (shrink)

The phrase “regenerative medicine” is used so often and for so many different things, with such enthusiasm or worry, and often with a sense that this is something radically new. This paper places studies of regeneration and applications in regenerative medicine into historical perspective. In fact, the first stem cell experiment was carried out in 1907, and many important lines of research have contributed since. This paper explores both what we can learn about the history and what we can learn (...) from the history of regenerative medicine research. (shrink)