The transcription factor CLAMP is required for neurogenesis in Drosophila melanogaster.

Neural stem cell (NSC) differentiation is controlled by cell-intrinsic and external signals from the stem cell niche including niche surface glia (SG). However, the mechanisms by which transcription factors drive NSC differentiation within the niche remain largely unknown. Here, we show that the Drosophila melanogaster transcription factor Chromatin-linked adaptor for MSL proteins (CLAMP) is required for regulation of stemness and proliferation of NSCs, especially in the optic lobe (OL). Using a validated clamp null mutant, we show that CLAMP promotes transcription of genes involved in stemness, proliferation, and glial development and represses transcription of genes involved in neurogenesis and niche survival. Consistent with transcriptional changes, CLAMP promotes NSC proliferation and niche SG production, while lack of CLAMP severely and specifically impacts OL development. To identify potential mechanisms by which CLAMP may regulate brain development, we examined CLAMP binding site motifs and available CLAMP ChIP-seq data to determine which genes may be direct versus indirect targets. We found that genes encoding Notch and tailless, both master regulators of brain development, are directly bound by CLAMP, indicating that they are key direct targets of CLAMP. Moreover, Notch and Tailless are critical for OL development, providing a mechanistic link to the severe deficits observed in OL development in the clamp null mutants. Overall, our results suggest that CLAMP regulates a core transcriptional program which drives NSC proliferation and differentiation via cell-intrinsic and niche-dependent mechanisms involving niche glia and transcriptional regulation of Notch and Tailless.