Basic helix-loop-helix (bHLH) family of transcription factors are key players of many developmental processes including neurogenesis. Roughly they can be divided into broadly expressed (class I) and others with tissue-specific expression. Class I members are capable of forming either homo- or heterodimers with tissue-specifically expressed bHLH transcription factors. There is a single member of class I HLH factors in Drosophila, daughterless (da), a homologoue to mammalian TCF4. In Pitt-Hopkins Syndrome (PHS), DNA binding domain of human TCF4 is a hot spot for mutations. Characterization of mutations showed that all the analyzed mutated TCF4 proteins have lost their ability to bind to their response elements but are still able to heterodimerize with their partners. This raises the possibility that PHS phenotype may be the result of both loss of function and gain of function of TCF4. Since Drosophila has a single homologue to TCF4, it is an excellent model system to study the function of wild type da and da with PHS mutations. Our aim is to study the function and target genes of daughterless in Drosophila larval and adult CNS development. More specifically we are going to (1) chart the expression of daughterless in larval and adult fly CNS; (2) analyse the consequences of altered da dosage to fly CNS development and function using hypomorphic mutant; (3) generate and test the da transgenic Drosophila model for PHS and (4) find novel target genes for da in Drosophila CNS.