Neurogenesis in Drosophila

Andrew Jarman, University of Edinburgh, Edinburgh, UK

Published online: January 2013

DOI: 10.1002/9780470015902.a0000825.pub2

Neurogenesis is the process by which neurons are born during the development of an animal. The nervous system entails great cellular diversity and is the most complex of any organ system. A developing animal needs to harness sophisticated cellular and genetic mechanisms to ensure the orderly generation of large numbers of neurons in the right places and times, and in the right numbers. A long history of molecular genetic studies in the fruit fly, Drosophila melanogaster, has provided many insights into how this is achieved. Neurogenesis involves the initial patterning of the ectoderm, the formation of neural precursor cells from the ectoderm and the formation of neurons from these precursors through fixed lineages involving asymmetric cell division. Many of the concepts uncovered apply to neurogenesis in other animals. Indeed, many of the molecular mechanisms are highly conserved.

Key Concepts:

  • The fruit fly has relatively few neurons in its nervous system, making it tractable to detailed developmental analysis.
  • The arrangement of these neurons is, as far as is known, very precisely determined by the mechanisms controlling neurogenesis during development.
  • Neurons are the progeny of neural precursor cells that derive from the ectoderm.
  • The precursor cells are specified by the action of proneural transcription factors, which are opposed by Notch signalling in the process of lateral inhibition.
  • At their formation, the precursors are already specified to contribute specific neuronal progeny via fixed lineages of cell division.
  • For the PNS, neural precursor identity is endowed by proneural factors, their cofactors.
  • For the CNS, neuroblasts have unique identities according to their location, due to their inheriting different combinations of ectodermal patterning factors.
  • Within the fixed division lineages, cellular diversity arises through asymmetric cell division, which is driven largely by asymmetrically localised and inherited cell fate determinants.

Keywords: cell type specification; neurogenesis; neuroblasts; sensory neurons; asymmetric cell division

Figure 1. Elements of the Drosophila larval nervous system. (a) This immunofluorescence image shows a young larva stained with antibodies that detect all neurons (magenta) and sensory neurons/axons (green). The CNS comprises the segmentally organised ventral nerve cord, which contains interneurons and cell bodies of the motor neurons, and the brain. In the body segments, the PNS comprises segmentally reiterated stereotypical patterns of body wall sensory neurons. In the head are numerous sensory neurons populating head sense organs. Axons of sensory and motor neurons make up dorsoventral nerves in each segment. (b) The pattern of sensory neurons in an abdominal segment. Type I neurons are associated with 4–5-celled sense organs. These include chemo- and mechano-sensory external sense organs (blue) and internal proprioceptive chordotonal organs (green). Type II neurons (red) have extensive dendritic trees associated with the epidermis. The pattern is so invariant that each neuron has its own name.
Figure 2. Overview of neurogenesis. (a) In the first stage, patterning mechanisms divide the early embryonic ectoderm into orthogonal DV and AP regions. For the AP (horizontal) axis, the ectoderm is first divided into segments, and then the segmentation genes subdivide each segment further (the expression of the segmentation genes is reiterated in each segment but is only depicted here in one segment). This grid system is used to define the locations of proneural clusters. (b) For the CNS, coincidence of segmentation and columnar genes acts to define proneural clusters of ventral (neuroectodermal) cells from which are selected the neuroblasts (the proneural cluster for neuroblast 5–6 is shown). The outcome is a stereotypical pattern of neuroblasts reiterated in each segment. (c) Each neuroblast divides reiteratively and asymmetrically to produce a chain of GMCs, each of which divides to generate two neurons. Each neuroblast therefore contributes an ordered group of neurons to that location of the CNS. (d) The PNS arises from the lateral ectoderm. As for the CNS, groups of cells form proneural clusters from which SOPs are selected (a single example is shown). Each SOP divides to form a specific sense organ in the body wall. Shown is a sensory bristle.
Figure 3. Notch signalling in sense organ precursor development. Cells in each proneural cluster express proneural factors (yellow), which endow each cell with the potential to become an SOP. In one cell, a higher level of proneural factor leads to production of Delta (Dl) protein. This activates the Notch (N) receptor on surrounding cells of the cluster. Subsequent intramembrane proteolysis releases the Notch intracellular domain (NICD), which enters the nucleus and binds to Supressor of Hairless (Su(H)), changing it from an transcriptional repressor to activator. This leads to activation of the E(spl) genes, which encode transcriptional repressors of the proneural genes. In consequence, only one cell of the proneural cluster retains its SOP potential and it is selected to become a SOP.
Figure 4. Sense organ development. SOPs divide stereotypically to produce the cells of the various sense organs. SOPs that arise in different locations within the lateral ectoderm are fated to generate the different sense organ types shown in Figure 1. Although the sense organs appear quite different from each other, each arises from a variant of a common cell lineage ‘ground plan’, reflecting an ancestral sense organ lineage pattern. The bristle and chordotonal organ lineages are very similar to each other, but the support cells differentiate differently to give the distinct sense organ types. The multidendritic neuron lineage appears quite distinct due to apoptosis of cells in all but one branch of the lineage.
Figure 5. Asymmetric cell division of neuroblasts. (a) Shown is a small portion of the ventral ectoderm in cross-section. When a new neuroblast emerges from the ectoderm, it inherits apical-basal polarity from its origin in the ectoderm via the apical localisation of the PAR complex proteins (the neuroblast is shown just leaving the ventral ectoderm, hence ‘apical’ and ‘basal’ are upside-down compared with their conventional representation). The neuroblast then expresses a number of cell fate determinants. Inscuteable and Pins localise apically with the PAR complex. (b) These proteins organise the apical-basal re-orientation of the mitotic spindle and simultaneously drive the adaptor protein Miranda to the basal cortex. Miranda binds the cell fate determinants Prospero and Brat (brain tumour), and also prospero mRNA via Staufen. (c) During cell division, all these determinants are inherited by the newly forming ganglion mother cell. (d) Upon cytokinesis, loss of Miranda releases Brat and Prospero to promote ganglion mother cell fate and repress cell division, so that this cell divides one last time to generate two neurons. The neuroblast is free to continue dividing to form further ganglion mother cells. The cycle continues with the re-expression of the determinants in the neuroblast in preparation for the next round of asymmetric cell division.
close
 References
    Bardin AJ, Le Borgne R and Schweisguth F (2004) Asymmetric localization and function of cell-fate determinants: a fly's view. Current Opinion in Neurobiology 14: 6–14.
    Bernardoni R, Kammerer M, Vonesch JL and Giangrande A (1999) Gliogenesis depends on glide/gcm through asymmetric division of neuroglioblasts. Developmental Biology 216: 265–275.
    Betschinger J, Mechtler K and Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124: 1241–1253.
    Blochlinger K, Jan LY and Jan YN (1991) Transformation of sensory organ identity by ectopic expression of Cut in Drosophila. Genes and Development 5: 1124–1135.
    Bossing T, Udolph G, Doe CQ and Technau GM (1996) The embryonic central nervous system lineages of Drosophila melanogaster. I. Neuroblast lineages derived from the ventral half of the neuroectoderm. Developmental Biology 179: 41–64.
    Broadus J, Fuerstenberg S and Doe CQ (1998) Staufen-dependent localization of prospero mRNA contributes to neuroblast daughter-cell fate. Nature 391: 792–795.
    Broadus J, Skeath JB, Spana EP et al. (1995) New neuroblast markers and the origin of the aCC/pCC neurons in the Drosophila central nervous system. Mechanisms of Development 53: 393–402.
    Brody T and Odenwald WF (2002) Cellular diversity in the developing nervous system: a temporal view from Drosophila. Development 129: 3763–3770.
    Cachero S, Simpson TI, zur Lage PI et al. (2011) The gene regulatory cascade linking proneural specification with differentiation in Drosophila sensory neurons. PLoS Biology 9: e1000568.
    Certel SJ and Thor S (2004) Specification of Drosophila motoneuron identity by the combinatorial action of POU and LIM-HD factors. Development 131: 5429–5439.
    Choksi SP, Southall TD, Bossing T et al. (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Developmental Cell 11: 775–789.
    Gomez-Skarmeta JL, Campuzano S and Modolell J (2003) Half a century of neural prepatterning: the story of a few bristles and many genes. Nature Reviews Neuroscience 4: 587–598.
    Hutterer A and Knoblich JA (2005) Numb and alpha-adaptin regulate Sanpodo endocytosis to specify cell fate in Drosophila external sensory organs. EMBO Reports 6: 836–842.
    Isshiki T, Pearson B, Holbrook S and Doe CQ (2001) Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell 106: 511–521.
    Jafar-Nejad H, Tien AC, Acar M and Bellen HJ (2006) Senseless and daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development 133: 1683–1692.
    Jarman AP, Grau Y, Jan LY and Jan YN (1993) atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell 73: 1307–1321.
    zur Lage PI, Prentice DRA, Holohan EE and Jarman AP (2003) The Drosophila proneural gene amos promotes olfactory sensillum formation and suppresses bristle formation. Development 130: 4683–4689.
    zur Lage PI, Simpson TI and Jarman AP (2011) Linking specification to differentiation: from proneural genes to the regulation of ciliogenesis. Fly 5: 322–326.
    Lai EC and Orgogozo V (2004) A hidden program in Drosophila peripheral neurogenesis revealed: fundamental principles underlying sensory organ diversity. Developmental Biology 269: 1–17.
    Martin-Bermudo MD, Martinez C, Rodriguez A and Jimenez F (1991) Distribution and function of the lethal of scute gene product during early neurogenesis in Drosophila. Development 113: 445–454.
    McDonald JA, Holbrook S, Isshiki T et al. (1998) Dorsoventral patterning in the Drosophila central nervous system: the vnd homeobox gene specifies ventral column identity. Genes and Development 12: 3603–3612.
    O'Connor-Giles KM and Skeath JB (2003) Numb inhibits membrane localization of Sanpodo, a four-pass transmembrane protein, to promote asymmetric divisions in Drosophila. Developmental Cell 5: 231–243.
    Overton PM, Meadows LA, Urban J and Russell S (2002) Evidence for differential and redundant function of the Sox genes dichaete and SoxN during CNS development in Drosophila. Development 129: 4219–4228.
    Powell LM and Jarman AP (2008) Context dependence of proneural bHLH proteins. Current Opinion in Genetics and Development 18: 411–417.
    Reeves N and Posakony JW (2005) Genetic programs activated by proneural proteins in the developing Drosophila PNS. Developmental Cell 8: 413–425.
    Rhyu MS, Jan LY and Jan YN (1994) Asymmetric distribution of numb protein during division of the sensory organ precursor cell confers distinct fates to daughter cells. Cell 76: 477–491.
    Rickert C, Kunz T, Harris KL, Whitington PM and Technau GM (2011) Morphological characterization of the entire interneuron population reveals principles of neuromere organization in the ventral nerve cord of Drosophila. Journal of Neuroscience 31: 15870–15883.
    Schmid A, Chiba A and Doe CQ (1999) Clonal analysis of Drosophila embryonic neuroblasts: neural cell types, axon projections and muscle targets. Development 126: 4653–4689.
    Shen CP, Jan LY and Jan YN (1997) Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell 90: 449–458.
    Simpson P (1997) Notch signalling in development: on equivalence groups and asymmetric developmental potential. Current Opinion in Genetics and Development 7: 537–542.
    Udolph G, Luer K, Bossing T and Technau GM (1995) Commitment of CNS progenitors along the dorsoventral axis of Drosophila neuroectoderm. Science 269: 1278–1281.
    Zhong W and Chia W (2008) Neurogenesis and asymmetric cell division. Current Opinion in Neurobiology 18: 4–11.
 Further Reading
    Doe CQ (2008) Neural stem cells: balancing self-renewal with differentiation. Development 135: 1575–1587.
    Jacob J, Maurange C and Gould AP (2008) Temporal control of neuronal diversity: common regulatory principles in insects and vertebrates? Development 135: 3481–3489.
    Orgogozo V and Grueber WB (2005) FlyPNS, a database of the Drosophila embryonic and larval peripheral nervous system. BMC Developmental Biology 5: 4.
    book Price DP, Jarman AP, Mason JO and Kind PC (2011) Building Brains: An Introduction to Neural Development. Chichester: Wiley-Blackwell.
    Skeath JB and Thor S (2003) Genetic control of Drosophila nerve cord development. Current Opinion in Neurobiology 13: 8–15.

Related Sub-Topics:

Nervous System Development | Development of Invertebrate Nervous System
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Neurogenesis in Drosophila
 
How to Cite close
Jarman, Andrew(Jan 2013) Neurogenesis in Drosophila. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000825.pub2]