“
“A brain contains many types of neurons that are derived from a limited number of progenitors (Truman and Bate, 1988 and Noctor et al., 2001). Most neural progenitors are destined to yield multiple neuron types. Interestingly, distinct neurons arise in specific temporal patterns in diverse model organisms. Although multiple mechanisms may act in sequence to ensure proper neuronal differentiation, it has become increasingly evident that neurons are born with defined birth-order/time-dependent

cell fate, generally referred to as neuronal temporal identity (Livesey and Cepko, 2001, Pearson and Doe, 2004, Batista-Brito et al., 2008, Jacob et al., 2008, Baek and Mann, 2009, Kao and Lee, 2010 and Okano and Temple, 2009). The relatively simple Drosophila brain develops Enzalutamide from a fixed number of neuroblasts (NBs) ( Truman and Bate, 1988 and Ito and Hotta, 1992). Most NBs make a characteristic set of neurons through the production of a series of ganglion mother cells (GMCs), which then divide once to deposit two neurons following each NB asymmetric cell division ( Knoblich, 2008 and Sousa-Nunes et al., 2010). Neurons of the same lineage origin remain clustered through development.

Such local and synchronized differentiation provides little room for the environment to diversify neurons born from the same progenitor. The congenital MAPK inhibitor endowment of different neuronal temporal identities probably underlies most, if not all, birth-order/time-dependent neuron type determinations in the Drosophila brain. Complete ADP ribosylation factor sequencing of a neural lineage (delineating neurons sequentially derived from a single progenitor) has substantiated the notion that every neuron was born with a predetermined fate contingent upon its birth order in the lineage. In the lineage that makes anterodorsal projection neurons (adPNs) of the antennal lobe (AL) (see Figure S1A available online), the progenitor deposits one AL PN at one time, as Notch-dependent

binary fate decision confers premature cell death on the other daughter cells of GMCs (Lin et al., 2010). Intriguingly, it yields 40 types of adPNs in an invariant sequence (Figure S1B) (Yu et al., 2010). The diverse adPNs, including 35 types of uniglomerular PNs and five types of polyglomerular PNs, can be distinguished based on their dendritic elaboration patterns in the AL. They also exhibit characteristic axon trajectories in the mushroom body (MB) and lateral horn (LH) (Jefferis et al., 2001, Marin et al., 2002, Marin et al., 2005, Wong et al., 2002 and Yu et al., 2010). Eighteen types of adPNs arise during embryogenesis, and the remaining 22 types are added through larval development. The embryonic-born adPNs, except the two VM3 glomerulus-targeting ones, are individually unique.