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SUMMARY:&quot\;Pathways specifying cell fates in the Drosophila CNS”.  -
  Stefan Thor\, Linkoping University\, Sweden
DTSTART:20160307T163000Z
DTEND:20160307T180000Z
UID:TALK62802@talks.cam.ac.uk
CONTACT:Lyn Dakin
DESCRIPTION:Baumgardt\, M.\, Miguel-Aliaga\, I.\, Karlsson\, D.\, Ekman\, 
 H.\, Thor\, S. (2007).  Specification of neuronal identities by feedforwar
 d combinatorial coding. PLos Biol 5(2): e37. doi:10.1371/journal.pbio.0050
 037.\n\nNeuronal specification is often seen as a multistep process: earli
 er regulators confer broad neuronal identity and are followed by combinato
 rial codes specifying neuronal properties unique to specific subtypes. How
 ever\, it is still unclear whether early regulators are re-deployed in sub
 type-specific combinatorial codes\, and whether early patterning events ac
 t to restrict the developmental potential of postmitotic cells. Here\, we 
 use the differential peptidergic fate of two lineage-related peptidergic n
 eurons in the Drosophila ventral nerve cord to show how\, in a feedforward
  mechanism\, earlier determinants become critical players in later combina
 torial codes. Amongst the progeny of neuroblast 5–6 are two peptidergic 
 neurons: one expresses FMRFamide and the other one expresses Nplp1 and the
  dopamine receptor DopR. We show the HLH gene collier functions at three d
 ifferent levels to progressively restrict neuronal identity in the 5–6 l
 ineage. At the final step\, collier is the critical combinatorial factor t
 hat differentiates two partially overlapping combinatorial codes that defi
 ne FMRFamide 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 pr
 oper neuropeptide gene. These results indicate that a limited number of re
 gulators may constitute a potent combinatorial code that dictates unique n
 euronal cell fate\, and that such codes show a surprising disregard for ma
 ny global instructive cues.\n\nBaumgardt\, M.\, Karlsson\, D.\, Terriente\
 , J.\, Dı´az-Benjumea\, F.J.\, Thor\, S. Neuronal subtype specification 
 within a lineage by opposing temporal feed-forward loops.\ndoi:10.1016/ j.
 cell.2009.10.032\n\nNeural progenitors generate distinct cell types at dif
 ferent 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 lineage
 s display broad temporal windows\, and it is unclear how broad windows pro
 gress into subwindows that generate unique cell types. We have addressed t
 his 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 spec
 ify a unique cell fate\, whereas the second loop suppresses the first loop
 \, thereby allowing for the generation of alternate cell fates. This mecha
 nism of temporal and ‘‘subtemporal’’ genes acting in opposing feed
 -forward loops may be used by many stem cell lineages to generate diversit
 y.\n\n
LOCATION:The Hodgkin Huxley Seminar Room\, Department of Physiology Develo
 pment and Neuroscience
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