articles
BSI Flies The Fly and the Brain
0
0
Research
In our laboratory we are investigating the genetic and cell-biological mechanisms by which neuron class fate choices are made and then translated into class-specific dendrite arbor shape, connectivity, and function. To address these fundamental problems we use genetics in two powerful model organisms, the fruit fly Drosophila melanogaster and the mouse.

How is neuron class-specific dendrite arbor shape generated?
Dendrites are the chief site of signal input into a neuron. Different neuron classes have dendrite arbors of different shapes, and it is generally accepted that these differences in shape are representative of the different computational abilities of neuron classes.

At the top of the genetic hierarchy controlling neuron development are transcription factors. Different neuron classes express different transcription factors, and it is these factors that shape neuron development to generate diversity. In the larval peripheral nervous system there are four main classes of multidendritic sensory neuron, of these the class IV neuron has a much bigger and more complex dendrite arbor than the others. We recently described a transcription factor code required to determine the characteristic dendrite arbor shape of the Drosophila class IV sensory multidendritic neuron (Jinushi-Nakao et al., 2007; Moore, 2008). We showed that two factors, Knot and Cut, interact together to control dendrite arbor shape, and each individually controls different aspects of the cytoskeleton. We further identified the microtubule severing protein Spastin, encoded by a gene that is often disrupted in hereditary spastic paraplegia, as an important component of the pathway through which the transcription factor Knot promotes the large and highly branched dendrite arbor shape of the class IV multidendritic neuron.

Uncovering transcription factors controlling neuron class-specific differentiation allows researchers to elucidate the developmental-genetic logic by which the mature functioning nervous system is formed. A significant new challenge is to identify the downstream effectors of these transcription factors.

The role of the PRDM oncogenes to define and maintain neural identity.

We originally identified the Prdm (PRDI-BF1 and RIZ homology domain containing) proto-oncogene transcription factor Hamlet as controlling a switch between neuron classes in Drosophila (Moore et al., 2002; Moore et al., 2004). Recent results from our lab have showed that the Prdm family are strong new candidates to act during mammalian CNS neurogenesis (Kinameri et al., 2008). As Prdm are new factors active in neurogenesis, they are likely to have molecular functions distinct from other known neurogenetic factors. Our studies of Prdm factors in neurogenesis may have wider-ranging importance; many Prdm family members are involved in blood formation and their misregulation can cause leukemia. Hence there may be conserved mechanisms of Prdm family member active in neurogenesis, hemopoiesis and oncogenesis.

 

.

0