"Pathways specifying cell fates in the Drosophila CNS”.

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• Stefan Thor, Linkoping University, Sweden
• Monday 07 March 2016, 16:30-18:00
• The Hodgkin Huxley Seminar Room, Department of Physiology Development and Neuroscience.

If you have a question about this talk, please contact Lyn Dakin.

Baumgardt, M., Miguel-Aliaga, I., Karlsson, D., Ekman, H., Thor, S. (2007). Specification of neuronal identities by feedforward combinatorial coding. PLos Biol 5(2): e37. doi:10.1371/journal.pbio.0050037.

Neuronal specification is often seen as a multistep process: earlier regulators confer broad neuronal identity and are followed by combinatorial codes specifying neuronal properties unique to specific subtypes. However, it is still unclear whether early regulators are re-deployed in subtype-specific combinatorial codes, and whether early patterning events act to restrict the developmental potential of postmitotic cells. Here, we use the differential peptidergic fate of two lineage-related peptidergic neurons in the Drosophila ventral nerve cord to show how, in a feedforward mechanism, earlier determinants become critical players in later combinatorial codes. Amongst the progeny of neuroblast 5–6 are two peptidergic neurons: one expresses FMR Famide and the other one expresses Nplp1 and the dopamine receptor DopR. We show the HLH gene collier functions at three different levels to progressively restrict neuronal identity in the 5–6 lineage. At the final step, collier is the critical combinatorial factor that differentiates two partially overlapping combinatorial codes that define FMR Famide versus Nplp1/DopR identity. Misexpression experiments reveal that both codes can activate neuropeptide gene expression in vast numbers of neurons. Despite their partially overlapping composition, we find that the codes are remarkably specific, with each code activating only the proper neuropeptide gene. These results indicate that a limited number of regulators may constitute a potent combinatorial code that dictates unique neuronal cell fate, and that such codes show a surprising disregard for many global instructive cues.

Baumgardt, M., Karlsson, D., Terriente, J., Dı´az-Benjumea, F.J., Thor, S. Neuronal subtype specification within a lineage by opposing temporal feed-forward loops. doi:10.1016/ j.cell.2009.10.032

Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS , a cascade of transcription factors, the ‘‘temporal gene cascade,’’ has been identified that acts to alter progenitor competence over time. However, many CNS lineages display broad temporal windows, and it is unclear how broad windows progress into subwindows that generate unique cell types. We have addressed this issue in an identifiable Drosophila CNS lineage and find that a broad castor temporal window is subdivided by two different feed-forward loops, both of which are triggered by castor itself. The first loop acts to specify a unique cell fate, whereas the second loop suppresses the first loop, thereby allowing for the generation of alternate cell fates. This mechanism of temporal and ‘‘subtemporal’’ genes acting in opposing feed-forward loops may be used by many stem cell lineages to generate diversity.

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