Visualization and Developmental analysis of Neural Circuitry

During brain development, neurons are generated in correct time and place, and form synaptic connections with correct targets.  These events are all essential for the normal brain function.  Thus, it is necessary to analyze the connectivity of neurons to understand what information they receive, process and transfer to other parts of the brain.  Zebrafish is an excellent model animal for this purpose, since

1) It is possible to visualize specific subsets of neurons in living animal by using cell-type specific promoter and fluorescent proteins such as GFP.

2) In combination with mutants and other tools such as antisense morpholino (MO), genes involved in the formation of neural circuitry could be identified.

Hindbrain is important for the animal survival by receiving many kinds of sensory information including somatosensory, octavolateral and visceral systems and by processing and transferring them to motor systems to generate adequate behavioral outputs.  Compared with our knowledge on the motor systems located on ventral side, including works from our laboratory using Islet-1:GFP fish, less is known on the development and connectivity of sensory systems located on the dorsal part.  To study the neural circuitry of dorsal hindbrain, we utilized promoter/enhancer of zic1, a zinc-finger transcription factor expressed in the dorsal neural tube.  We made a PAC transgenic fish which expresses GFP by utilizing Gal4VP16/UAS system (Fig. 1).  GFP-positive neurons are mainly commissural and project to two distinct targets, torus semicircularis (TS) in the midbrain and contralateral hindbrain.  They likely correspond to projection neurons that constitute octavolateral nucleus.  Morpholino experiments showed that bHLH transcription factor atoh1a is essential for the development of neurons projecting to the TS.  Interestingly, neurons projecting to the contralateral hindbrain are inhibitory, possibly play a role to enhance signal-to-noise ratio (Fig. 2).

Fig. 1 @@@@@@@@@@Fig. 2

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Takayuki Sassa


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