The major function of the brain is to translate/integrate neuronal functions to produce behaviors, making the complexity of the central nervous system both mysterious and fascinating. The proper functioning of the brain relies not only on the generation of the vast repertoire of distinct neural (neurons and glia) types but also on its meticulous neural circuitry. However, how these neural populations are specified, differentiated, and organized into networks with various functions remains a topic of interest. Various cellular and molecular programs known to generate neural diversity may also play a major role in establishing appropriate neural connectivity.

Modern genetic and molecular techniques have allowed researchers to better understand generation of neural diversity; various invertebrate animal models, such as D. melanogaster and C. elegans, as well as vertebrate model systems, have provided mediums by which genetics of developmental processes can be tracked and observed. The ultimate goal of these animal model studies is to relate conserved neurodevelopmental mechanisms to human physiology and pathology [1], [2], [3], [4]. Altogether, these scientific tools may be utilized to understand every detail of central nervous system development, starting from the earliest stem cell to the highly compartmentalized systems in the mature brain. Despite having fewer neurons (~100, 000) than the mammalian brain (86 billion in humans), the Drosophila brain supports a range of complex behaviors [5].

Understanding the development of neural diversity and its role in establishing complex circuits is essential for eliciting function, underlying behavior, and higher order cognition. The immense diversity of neurons and glia established during development is responsible for ensuring the proper functionality of the central nervous system (CNS). [6], [7], [8], [9], [10]. Drosophila neural stem cells (NSCs, also known as neuroblasts) divide asymmetrically to self-renew and produce differentiated progeny of diverse types [11], [12]. Based on the division pattern, NSCs are categorized into type 0, type I, and type II lineages [11], [13], [14], [15], [16]. Type 0 NSCs self-renew to produce another NSC and two additional differentiated neurons and/or glia, and type I NSCs self-renew and produce one ganglion mother cell (GMC), which terminally divides to produce two neurons and/or glia [11]. In contrast, type II NSCs have evolved a special amplification division pattern: they divide to self-renew and produce a transit-amplifying intermediate neural progenitor (INP) [13], [16], [17]. Based on current knowledge, each INP divides approximately 4–6 times and generates a total of around 6 GMCs to expand and diversify the neural populations of the adult brain [16], [18], [19], [20], [21], [22]. This unique division mode allows type II NSCs to amplify neural progeny populations 3–4 times more than type I NSCs (Fig. 1A). Interestingly, type II NSCs are similar to mammalian outer radial glial cells (oRGCs) in the outer subventricular zone (OSVZ) in their division pattern (Fig. 1B). The oRGCs are responsible for generating the diverse neural populations of the cortex via transit- amplifying INPs [6], [8], [9], [16], [22], [23], [24], [25], [26]. Furthermore, the considerable range of neural diversity found in both flies and mammals is only possible because of the intricate signaling mechanisms, hormonal cues, and tightly controlled spatiotemporal gene expression in neural progenitors during development [8], [11], [22], [27], [28], [29], [30], [31], [32], [33], [34], [35].

Larval type II NSCs generate the neurons that lpredominantly populate the central complex, which makes up the bulk of the sensory and locomotion centers [19], [36], [37], [38]. In the following sections, we will focus on the central brain NSCs of D. melanogaster larvae with an emphasis on type II NSCs (Fig. 2 A). Additionally, we will summarize recent findings relating to temporal patterning of type II lineages and the mechanisms that diversify the lineages which populate the adult central complex. Towards the end, we will discuss possible ways to link temporal patterning to neural identity, connectivity, circuit formation, and function.