[AQ1] [AQ2] [AQ5] [AQ6] [AQ7] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 1 Review Composition of a Neuromere and Its Segmental Diversification under the Control of Hox Genes in the Embryonic CNS of Drosophila Gerhard M. Technau, Ana Rogulja-Ortmann, Christian Berger, Oliver Birkholz and Christof Rickert Institute of Genetics, University of Mainz, Mainz, Germany Abstract: Studies performed at the level of single, identifed cells in the fruitfy Drosophila have decisively contributed to our understanding of the mechanisms underlying the development and function of the nervous system. This review highlights some of the work based on single-cell analyses in the embryonic/larval CNS that sheds light on the principles underlying formation and organization of an entire segmental unit and its divergence along the anterior-posterior body axis. Keywords: cell lineage, CNS, Drosophila, Hox genes, single-cell tracing, segmental patterning A major goal in developmental neurobiology is to understand how a large number of different neural cell types is generated and assembled into functional circuits. As a prerequisite for approaching the mecha- nisms that orchestrate both formation and function of neural circuits, the constituent cells of the CNS need to be individually identified, thoroughly described, and their origin should be clarified. The relatively simply structured embryonic/larval ventral nerve cord (VNC) of Drosophila is a suitable model system to reach this goal. Embryonic development of the Drosophila CNS can be subdivided into four major phases (Figure 1): 1) The neurogenic regions of the ectoderm are determined in the blastoderm using the products of early dorso/ventral and anterior/posterior patterning genes (St Johnston & Nüsslein-Volhard, 1992; Biehs et al., 1996), the ventral neurogenic region representing the anlage of the VNC, the procephalic neurogenic region that of the brain. 2) Within the neuroectoderm proneural and neurogenic genes con- trol the selection of cells that will, upon gastrulation, delaminate as CNS progenitor cells, called neuroblasts (NBs) (e.g. reviewed by Artavanis-Tsakonas & Simpson, 1991; Campos-Ortega, 1995). 3) NBs typically divide in a stem cell mode to produce a chain of smaller gan- glion mother cells, which are generally dividing once to give rise to two postmitotic progeny cells. 4) Progeny cells differentiate into specific neuronal and glial cell types or/and undergo programmed cell death (PCD; e.g. Rogulja-Ortmann et al., 2007). A subpopulation of the NBs enters a phase of quiescence and become reactivated in the larva to produce the cells of the adult CNS; the oth- ers undergo PCD or terminal differentiation. These processes take place in a coordinated manner along the anterior-posterior body axis to form segmental units of the CNS, called neuromeres. Whereas neuromeres of the brain, the gnathal, and the most posterior abdomi- nal (A8–A10) segments are derived to various degrees, the thoracic (T1–T3) and anterior abdominal neuromeres (A1–A7) in the embryo are very similar to each other and resemble the ground state (T2, which does not require input from any Hox genes; Lewis, 1978) . In the following, we will give an overview of some recent work directed towards dissecting the embryonic (larval) CNS down to the level of single identified cells and their lineages, and towards analysing the mechanisms that control patterning of the CNS along the anterior- posterior body axis. TYPES AND ARRANGEMENT OF CONSTITUENT CELLS OF A TYPICAL NEUROMERE IN THE VNC In the late embryo a typical neuromere (T1–A7) consists of approximately 340 postmitotic cells on either side (plus Received 25 October 2013; accepted 18 November 2013. Address correspondence to Dr Gerhard M. Technau, Institute of Genetics, University of Mainz, D-55099 Mainz, Germany. E-mail: technau@uni-mainz.de J. Neurogenetics, Early Online: 1–10 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 0167-7063 print/1563-5260 online DOI: 10.3109/01677063.2013.868459 GNEG_A_868459.indd 1 GNEG_A_868459.indd 1 6/18/2014 5:01:24 PM 6/18/2014 5:01:24 PM