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 of the optic lobe (OL). 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. Το identify potential mechanisms by which CLAMP may regulate brain development, we examined CLAMP motifs and available CLAMP ChIP-seq data to determine which genes may be direct versus indirect targets. CLAMP motifs are present at many target genes including the glial-determining gene, glial cells missing, while Tailless, the master regulator of OL-development is directly bound by CLAMP. In accordance to these results, in larval OL NSCs lacking CLAMP, Tailless levels are decreased dramatically, suggesting that CLAMP controls OL neurogenesis via Tailless. Overall, our results suggest that CLAMP regulates a transcriptional program which drives NSC proliferation and differentiation via cell-intrinsic and niche-dependent mechanisms that involve transcriptional regulation of Tailless and niche glia.