Drosophila embryonic type II neuroblasts: origin, temporal patterning, and contribution to the adult central complex

Abstract

16Drosophila neuroblasts are an excellent model for investigating how neuronal diversity is 17 generated. Most brain neuroblasts generate a series of ganglion mother cells (GMCs) that each 18 make two neurons (type I lineage), but sixteen brain neuroblasts generate a series of intermediate 19 neural progenitors (INPs) that each produce 4-6 GMCs and 8-12 neurons (type II lineage). Thus, 20 type II lineages are similar to primate cortical lineages, and may serve as models for 21 understanding cortical expansion. Yet the origin of type II neuroblasts remains mysterious: do 22 they form in the embryo or larva? If they form in the embryo, do their progeny populate the adult 23 central complex, as do the larval type II neuroblast progeny? Here we present molecular and 24 clonal data showing that all type II neuroblasts form in the embryo, produce INPs, and express 25 known temporal transcription factors. Embryonic type II neuroblasts and INPs undergo 26 quiescence, and produce embryonic-born progeny that contribute to the adult central complex. 27 Our results provide a foundation for investigating the development of the central complex, and 28 tools for characterizing early-born neurons in central complex function. 29 30 31 KEY WORDS: neurogenesis, type II neuroblast, intermediate neural progenitors, INPs, temporal 32 patterning, Pdm, Castor, Grainy head, Dichaete, central complex 33 65 2015). Second, the temporal transcription factors Hunchback (Hb), Krüppel (Kr), Nubbin/Pdm2 66 (Pdm), Castor (Cas) and Grainy head (Grh) specify unique GMC identities within each neuroblast 67 3 lineage (Brody and Odenwald, Moris-Sanz et al., 2014). In contrast, much less is known 71 about type II neuroblasts. Only one of the eight type II neuroblasts has been identified in the 72 embryo (Hwang and Rulifson, 2011); the origin of the other type II neuroblasts has not been 73 reported in existing embryonic brain neuroblast maps (Urbach and Technau, 2003). It remains 74 unknown whether type II neuroblasts arise de novo from the neuroectoderm similar to type I 75 neuroblasts, or whether they arise from a type I > type II transition similar to the type I > type 0 76 neuroblast transitions (Baumgardt et al., 2014; Bertet et al., 2014). If type II neuroblasts form 77 during embryogenesis, it is unknown whether they utilize the same Hb > Kr > Pdm > Cas > Grh 78 temporal transcription factor cascade to generate neuronal diversity, or whether they make 79 embryonic born INPs that sequentially express Dichaete (D) > Grh > Eyeless similar to larval 80 INPs (Bayraktar and Doe, 2013). Furthermore, if type II neuroblast lineages are initiated in the 81 embryo, it would be interesting to know if their INPs undergo quiescence, similar to type I and II 82 neuroblasts; if so they would be the only cell type beyond neuroblasts known to enter quiescence 83 at the embryo/larval transition. Perhaps most importantly, identifying embryonic type II 84 neuroblasts is essential for subsequent characterization of their early-born progeny, which are 85 likely to gen...

Developmentally Arrested Precursors of Pontine Neurons Establish an Embryonic Blueprint of the Drosophila Central Complex

“…Four bilateral pairs of lineages, DM1-DM4, located in the posterior brain cortex (top), generate the columnar neurons whose axons (gray bars and lines oriented along the vertical axis; filled circles symbolize terminal arborizations) interconnect the compartments of the central complex in a strict topographical order. The location of DM1-DM4 cell bodies within the cortex is reflected in the position at which their corresponding tracts enter and terminate within the central complex (20)(21)(22)(23), as indicated by the color code. DM1 axons (blue) enter through the medial segments of the PB (1-3, after [8]), followed by DM2 (green, PB segments 4 to 5), DM3 (red, segments 6 to 7), and DM4 (yellow, segments 8 to 9).…”

“…Thus, in the embryo, the apical (superficial) versus basal (deep) location of a neuron reflects its birthdate, because proliferating neuroblasts are always located at the surface. However, neuronal cell bodies reshuffle during the pronounced thinning of the cortex that occurs during the embryo-larva transition [22], and the original position of a neuron is lost. This explains why measurements of the distance between cell body and neuropil surface for SU neurons, compared to differentiated neurons, for 10 representative lineages yielded no significant difference in apical versus basal position of SU neurons versus differentiated neurons (data not shown).…”

“…Remarkably, the central complex, as defined anatomically for the adult, is the one major set of compartments of the fly brain that lacks a larval counterpart. Thus, the large majority of tangential and columnar neurons with their highly ordered connections outlined above are secondary neurons born in the larva [20], even though the four DM lineages have been distinguished in the embryo [21][22][23]. This prompts the question of what guidance mechanisms control central complex connectivity and what part primary neurons play during this process.…”

Genetic Mechanisms Regulating the Spatiotemporal Modulation of Proliferation Rate and Mode in Neural Progenitors and Daughter Cells during Embryonic CNS Development

“…In the brain hemisegments combined (B1-B3) about 106 NBs delaminate from the anterior neuroectoderm. Recently, another 8 NBs which divide in Type II mode (see below for division modes) have been identified in the embryonic brain [112,113], so in total there are 114 NBs in the B1-B3 hemisegments.…”

“…15). Embryonic Type II NBs have been recently identified in the brain and have been shown to contribute tremendously to the adult CNS [112,113].…”