Origin ofDrosophilamushroom body neuroblasts and generation of divergent embryonic lineages

Abstract

Key to understanding the mechanisms that underlie the specification of divergent cell types in the brain is knowledge about the neurectodermal origin and lineages of their stem cells. Here, we focus on the origin and embryonic development of the four neuroblasts (NBs) per hemisphere in Drosophila that give rise to the mushroom bodies (MBs), which are central brain structures essential for olfactory learning and memory. We show that these MBNBs originate from a single field of proneural gene expression within a specific mitotic domain of procephalic neuroectoderm, and that Notch signaling is not needed for their formation. Subsequently, each MBNB occupies a distinct position in the developing MB cortex and expresses a specific combination of transcription factors by which they are individually identifiable in the brain NB map. During embryonic development each MBNB generates an individual cell lineage comprising different numbers of neurons, including intrinsic γ-neurons and various types of non-intrinsic neurons that do not contribute to the MB neuropil. This contrasts with the postembryonic phase of MBNB development during which they have been shown to produce identical populations of intrinsic neurons. We show that different neuron types are produced in a lineage-specific temporal order and that neuron numbers are regulated by differential mitotic activity of the MBNBs. Finally, we demonstrate that γ-neuron axonal outgrowth and spatiotemporal innervation of the MB lobes follows a lineage-specific mode. The MBNBs are the first stem cells of the Drosophila CNS for which the origin and complete cell lineages have been determined.

The p21-activated kinase Mbt is a component of the apical protein complex in central brain neuroblasts and controls cell proliferation

“…demonstrate that mbt mutant MBNBs and their progeny express their characteristic combination of transcription factors and, thus, show correct cell fate specification (Kunz et al, 2012). They can sequentially generate all different Kenyon cell subtypes, which differentiate properly and survive until adulthood.…”

“…Both indicate a role in mushroom body (MB) development. In addition, MBNBs and their lineages are to date the only central brain neuroblast lineages characterized from their embryonic origin until the imago, making them an ideal model system (Kunz et al, 2012). In each brain hemisphere, four MBNBs continuously divide from embryonic until late pupal stages to generate all different subtypes of MB neurons (Kenyon cells) in a sequential manner (Ito and Hotta, 1992;Ito et al, 1997;Lee et al, 1999).…”

“…In each brain hemisphere, four MBNBs continuously divide from embryonic until late pupal stages to generate all different subtypes of MB neurons (Kenyon cells) in a sequential manner (Ito and Hotta, 1992;Ito et al, 1997;Lee et al, 1999). The embryonic MBNBs are individually characterized by their enlarged size, their distinct position within the brain cortex and the specific expression of a set of transcription factors; thus, they are readily identifiable (Kunz et al, 2012). type embryos, and also Ey/Dac expression in the respective γ-neurons was largely normal, although their final number is reduced (Fig.…”

Clonal Development and Organization of the Adult Drosophila Central Brain

“…The existence of 4 highly similar yet distinct MB lineages [40] suggests that expansion of brain anatomy during insect evolution has involved reuse of existing NB fating programs [41]. Such mechanisms may explain the derivation of neurons of the same class from hemilineages of distinct NB origin such as uniglomerular PNs from the ALl and ALad lineages.…”

Labeling of Single Cells in the Central Nervous System of <em>Drosophila melanogaster</em>

“…It reveals the morphology of neural processes in great detail (Figure 4). One of the major advantages of the method is that it enables the morphology of virtually any type of neuron in the CNS to be examined (for the embryonic ventral nerve cord, see Rickert et al, 2011; for the embryonic brain, see Kunz et al, 2012). In addition, it does not require complex combinations of genetic elements to be present in the embryo, as several of the genetic labeling techniques do.…”