Dataset Information

Drosophila Tey represses transcription of the repulsive cue Toll and generates neuromuscular target specificity.

ABSTRACT: Little is known about the genetic program that generates synaptic specificity. Here we show that a putative transcription factor, Teyrha-Meyhra (Tey), controls target specificity, in part by repressing the expression of a repulsive cue, Toll. We focused on two neighboring muscles, M12 and M13, which are innervated by distinct motoneurons in Drosophila. We found that Toll, which encodes a transmembrane protein with leucine-rich repeats, was preferentially expressed in M13. In Toll mutants, motoneurons that normally innervate M12 (MN12s) formed smaller synapses on M12 and instead appeared to form ectopic nerve endings on M13. Conversely, ectopic expression of Toll in M12 inhibited synapse formation by MN12s. These results suggest that Toll functions in M13 to prevent synapse formation by MN12s. We identified Tey as a negative regulator of Toll expression in M12. In tey mutants, Toll was strongly upregulated in M12. Accordingly, synapse formation on M12 was inhibited. Conversely, ectopic expression of tey in M13 decreased the amount of Toll expression in M13 and changed the pattern of motor innervation to the one seen in Toll mutants. These results suggest that Tey determines target specificity by repressing the expression of Toll. These results reveal a mechanism for generating synaptic specificity that relies on the negative regulation of a repulsive target cue.

SUBMITTER: Inaki M

PROVIDER: S-EPMC2882133 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Drosophila Tey represses transcription of the repulsive cue Toll and generates neuromuscular target specificity.

Inaki Mikiko M Shinza-Kameda Makiko M Ismat Afshan A Frasch Manfred M Nose Akinao A

Development (Cambridge, England) 20100526 13

Little is known about the genetic program that generates synaptic specificity. Here we show that a putative transcription factor, Teyrha-Meyhra (Tey), controls target specificity, in part by repressing the expression of a repulsive cue, Toll. We focused on two neighboring muscles, M12 and M13, which are innervated by distinct motoneurons in Drosophila. We found that Toll, which encodes a transmembrane protein with leucine-rich repeats, was preferentially expressed in M13. In Toll mutants, motone ...[more]

PMID: 20504957

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Project description:Proper neural function depends on the correct specification of individual neural fates, controlled by combinations of neuronal transcription factors. Different neural types are sequentially generated by neural progenitors in a defined order, and this temporal patterning process can be controlled by Temporal Transcription Factors (TTFs) that form temporal cascades in neural progenitors. The Drosophila medulla, part of the visual processing center of the brain, contains more than 70 neural types generated by medulla neuroblasts which sequentially express several TTFs, including Homothorax (Hth), eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D) and Tailless (Tll). However, it is not clear how such a small number of TTFs could give rise to diverse combinations of neuronal transcription factors that specify a large number of medulla neuron types. Here we report how temporal patterning specifies one neural type, the T1 neuron. We show that the T1 neuron is the only medulla neuron type that expresses the combination of three transcription factors Ocelliless (Oc or Otd), Sox102F and Ets65A. Using CRISPR-Cas9 system, we show that each transcription factor is required for the correct morphogenesis of T1 neurons. Interestingly, Oc, Sox102F and Ets65A initiate expression in neurons beginning at different temporal stages and last in a few subsequent temporal stages. Oc expressing neurons are generated in the Ey, Slp and D stages; Sox102F expressing neurons are produced in the Slp and D stages; while Ets65A is expressed in subsets of medulla neurons born in the D and later stages. The TTF Ey, Slp or D is required to initiate the expression of Oc, Sox102F or Ets65A in neurons, respectively. Thus, the neurons expressing all three transcription factors are born in the D stage and become T1 neurons. In neurons where the three transcription factors do not overlap, each of the three transcription factors can act in combination with other neuronal transcription factors to specify different neural fates. We show that this way of expression regulation of neuronal transcription factors by temporal patterning can generate more possible combinations of transcription factors in neural progeny to diversify neural fates.

Dataset Information

Drosophila Tey represses transcription of the repulsive cue Toll and generates neuromuscular target specificity.

Publications

Drosophila Tey represses transcription of the repulsive cue Toll and generates neuromuscular target specificity.

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