Cell lineage and cell fate specification in the embryonic CNS of Drosophila Joachim Urban and Gerhard M. Technau The Drosophila CNS derives from a population of neural stem cells, called neuroblasts (NBs), which delaminate individually from the neurogenic region of the ectoderm. In the embryonic ventral nerve cord each NB can be uniquely identified and gives rise to a specific lineage consisting of neurons and/ or glial cells. This ‘NB identity’ is dependent on the position of the progenitor cells in the neuroectoderm before delamination. The positional information is provided by the products of segment polarity and dorsoventral (D/ V) pattern- in g gen es. Su bsequ en tly, ‘cell fate gen es’ like huckebein (hkb) and eagle (eg) contribute to the generation of specific NB lineages. T hese genes act downstream of segment polarity and D/ V patterning genes and regulate different processes such as the generation of glial cells and the determin ation of seroton ergic n eu ron s. Key words: CNS cell fate / Drosophila / glia / neuroblast lineage / serotonergic neurons ©1997 Academic Press Ltd Early neurogenesis in Drosophila The embryonic development of the central nervous system (CNS) in vertebrates as well as invertebrates is a process whereby a two-dimensional ectodermal cell layer is transformed into a highly organized three- dimensional array consisting of a large number of different types of neurons and glia. To unravel the mechanisms underlying this highly regulated process, Drosophila represents a useful model system. In all species the CNS derives from the ectodermal neurogenic region (NR). In Drosophila the proce- phalic NR gives rise to the brain whereas the ventral nerve cord derives from the ventral NR (Figure 1A). The structure of the brain is very complex and in contrast to the ventral nerve cord its development is poorly understood. In the following we will focus on aspects of the embryonic development of the ventral nerve cord (VNC). It is reasonable to assume that the principle mechanisms of neurogenesis are rather similar between head and trunk. In addition to the ventral neuroectoderm there are other cells involved in the generation of the VNC: the mesectodermal cells. These cells form a single row on either side between the anlagen of the mesoderm and the neuroectoderm. During gastrulation the meso- derm invaginates so that both rows of mesectodermal cells merge along the ventral midline (Figure 1A, right). Single cell cultures of neuroectodermal as well as mesectodermal cells give rise to neural progeny, whereas single cultured dorsal ectodermal cells pro- duce epidermal cells. 1 This shows that each ecto- dermal cell has an intrinsic neurogenic or epidermo- genic bias depending on dorsoventral positional information. If in the embryo these cells strictly followed their intrinsic properties, the cells of the neuroectoderm would exclusively develop as neural progenitors. However, in the neuroectoderm of Drosophila only around 25% of the cells delaminate as neuroblasts (NB) whereas the other 75% develop as epidermo- blasts. NB delamination begins at the early gastrula stage and proceeds in a defined spatial and temporal pattern. 2,3 Cell ablation experiments in the grass- hopper as well as cell transplantations in Drosophila showed that the decision between a neural and non- neural cell fate depends on cell–cell interactions. 4-6 Intensive work on this subject over recent years has led to a deeper understanding of the mechanisms controlling this decision. 7 There are two groups of genes mainly involved in this process: the proneural genes 8,9 and the neurogenic genes. 10-12 All known proneural genes code for transcription factors having a basic Helix Loop Helix (bHLH) domain. They are necessary to impose a neural fate onto neuroecto- dermal cells and consequently loss of function muta- tions of proneural genes lead to a lack of NBs. 13-15 The proneural genes are expressed in small groups of 4 to From the Institut f¨ ur Genetik, Universit¨ at Mainz, Saarstraße 21 D-55122, Mainz, Germany seminars in CELL &DEVELOPMENTAL BIOLOGY, Vol 8, 1997: pp 391–400 ©1997 Academic Press Ltd 1084-9521/97/040391 + 10 $25.00/0/sr970163 391