By contrast, when the same progenitor resumes proliferation in early larvae, it yields multiple identical neurons before transiting to produce a different neuron type. Strikingly, distinct adPN types show different reproducible cell counts (Yu et al., 2010). This stereotyped developmental blueprint clearly indicates that the neuronal birth order strictly dictates the fate of each neuron made through about 80 rounds of NB self-renewal.
What molecular mechanisms may specify so many neuron types with such fine temporal precision? The transcriptional cascade of Hunchback (Hb), Kruppel (Kr), POU domain proteins 1 and 2 (Pdm), and Castor (Cas) is known to specify the first several neurons across NB lineages in the embryonic ventral ganglion (for reviews, see Pearson and Doe, 2004 and Jacob et al., 2008). The
same transcriptional cascade or its variants may reiterate to specify additional neuron check details fates at later time points. Further, a single temporal factor may trigger discrete feedforward regulatory networks in the contiguously derived siblings to diversify neuron fates (Baumgardt et al., 2007 and Baumgardt et al., 2009). Although their involvement in the Drosophila central brain remains elusive, the Chinmo BTB-zinc finger nuclear protein was recently found to govern neuronal temporal identity in MB lineages via a different mechanism ( Zhu et al., 2006). Chinmo proteins exist among the sequentially derived MB neurons in a high-to-low temporal gradient that dictates
multiple MB temporal Bioactive Compound Library solubility dmso fates based during on the levels of Chinmo expression. The temporal gradient of Chinmo is established via a 5′ untranslated region (5′ UTR)-dependent translational control, and one can reproducibly elicit MB temporal cell-fate transformation in either direction by modulating Chinmo expression in newborn neurons. Determining Chinmo’s role(s) in additional neural lineages has revealed that it may govern neuronal temporal identity in lineage-specific manners. In a serial production of six distinct central complex neurons, Chinmo is specifically required in the third sibling for not adopting the fourth temporal cell fate ( Yu et al., 2009). And our earlier analysis of Chinmo function in the adPN lineage had been limited to the first larval-born adPN type, which was uniformly transformed to the fourth larval-born adPN type in the absence of Chinmo ( Zhu et al., 2006). To elucidate how numerous temporal fates could be invariably specified through a protracted neuronal lineage, we determined the role of known temporal fating factors, including Chinmo and the Hb/Kr/Pdm/Cas transcriptional cascade, in the serial production of 40 adPN types. We found that Chinmo governs neuronal temporal identity in two separate windows of adPN production. Chinmo acts to suppress the next Chinmo-independent temporal fate among all neurons born within each Chinmo-dependent window.