From temporal patterning to neuronal connectivity in Drosophila type I neuroblast lineages.

The development of the central nervous system (CNS) in flies and mammals requires the production of distinct neurons in different locations and times. Here we review progress on how Drosophila stem cells (neuroblasts; NBs) generate distinct neurons over time. There are two types of NBs: type I and type II NBs (defined below); here we focus on type I NBs; type II NBs are reviewed elsewhere in this issue. Type I NBs generate neural diversity via the cascading expression of specific temporal transcription factors (TTFs). TTFs are sequentially expressed in neuroblasts and required for the identity of neurons born during each TTF expression window. In this way TTFs specify the "temporal identity" or birth-order dependent identity of neurons. Recent studies have shown that TTF expression in neuroblasts alter the identity of their progeny, including directing motor neurons to form proper connectivity to the proper muscle targets, independent of their birth-order. Similarly, optic lobe (OL) type I NBs express a series of TTFs that promote proper neuron morphology and targeting to the four OL neuropils. Together, these studies demonstrate how temporal identity is crucial in promoting proper circuit assembly within the Drosophila CNS. In addition, TTF orthologs in mouse are good candidates for specifying neuron types in the neocortex and retina. In this review we highlight the recent advances in understanding the role of TTFs in CNS circuit assembly in Drosophila and reflect on the conservation of these mechanisms in mammalian CNS development.

The Hunchback temporal transcription factor determines motor neuron axon and dendrite targeting in Drosophila.

The generation of neuronal diversity is essential for circuit formation and behavior. Morphological differences in sequentially born neurons could be due to intrinsic molecular identity specified by temporal transcription factors (henceforth called intrinsic temporal identity) or due to changing extrinsic cues. Here, we have used the Drosophila NB7-1 lineage to address this issue. NB7-1 generates the U1-U5 motor neurons sequentially; each has a distinct intrinsic temporal identity due to inheritance of different temporal transcription factors at its time of birth. We show that the U1-U5 neurons project axons sequentially, followed by sequential dendrite extension. We misexpressed the earliest temporal transcription factor, Hunchback, to create 'ectopic' U1 neurons with an early intrinsic temporal identity but later birth-order. These ectopic U1 neurons have axon muscle targeting and dendrite neuropil targeting that are consistent with U1 intrinsic temporal identity, rather than with their time of birth or differentiation. We conclude that intrinsic temporal identity plays a major role in establishing both motor axon muscle targeting and dendritic arbor targeting, which are required for proper motor circuit development.