ArticleBiology open2015
Introducing Pitt-Hopkins syndrome-associated mutations of TCF4 to Drosophila daughterless.
Article in Biology open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration.Nature communications · 2025Article
- An attempt to explain what intrinsically disordered TCF4 does in its spare time when PTHS-related mutations prevent it from doing its job.Cell communication and signaling : CCS · 2025Review
- Surgical treatment of Pitt-Hopkins syndrome associated with strabismus and early-onset myopia: Two case reports.World journal of clinical cases · 2022Article
- Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders inInternational journal of molecular sciences · 2022Review
- Expression of alternative transcription factor 4 mRNAs and protein isoforms in the developing and adult rodent and human tissues.Frontiers in molecular neuroscience · 2022Article
- Functional consequences of TCF4 missense substitutions associated with Pitt-Hopkins syndrome, mild intellectual disability, and schizophrenia.The Journal of biological chemistry · 2021Article
- Pitt-Hopkins syndrome: phenotypic and genotypic description of four unrelated patients and structural analysis of corresponding missense mutations.Neurogenetics · 2021Article
- Molecular and Cellular Function of Transcription Factor 4 in Pitt-Hopkins Syndrome.Developmental neuroscience · 2021Review
- Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks.International journal of molecular sciences · 2020Review
- Daughterless, theDisease models & mechanisms · 2020Article
- Genetic interaction screen for severe neurodevelopmental disorders reveals a functional link between Ube3a and Mef2 in Drosophila melanogaster.Scientific reports · 2020Article
- Structural basis for preferential binding of human TCF4 to DNA containing 5-carboxylcytosine.Nucleic acids research · 2019Article
- Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series.Journal of child neurology · 2018Review
- Common Pathophysiology in Multiple Mouse Models of Pitt-Hopkins Syndrome.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- The Intellectual Disability and Schizophrenia Associated Transcription Factor TCF4 Is Regulated by Neuronal Activity and Protein Kinase A.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- A case of Pitt-Hopkins syndrome presented with Angelman-like syndromic phenotypes.BioMedicine · 2016Article
- Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons.Cell reports · 2016Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Pitt-Hopkins syndrome (PTHS) is caused by haploinsufficiency of Transcription factor 4 (TCF4), one of the three human class I basic helix-loop-helix transcription factors called E-proteins. Drosophila has a single E-protein, Daughterless (Da), homologous to all three mammalian counterparts. Here we show that human TCF4 can rescue Da deficiency during fruit fly nervous system development. Overexpression of Da or TCF4 specifically in adult flies significantly decreases their survival rates, indicating that these factors are crucial even after development has been completed. We generated da transgenic fruit fly strains with corresponding missense mutations R578H, R580W, R582P and A614V found in TCF4 of PTHS patients and studied the impact of these mutations in vivo. Overexpression of wild type Da as well as human TCF4 in progenitor tissues induced ectopic sensory bristles and the rough eye phenotype. By contrast, overexpression of Da(R580W) and Da(R582P) that disrupt DNA binding reduced the number of bristles and induced the rough eye phenotype with partial lack of pigmentation, indicating that these act dominant negatively. Compared to the wild type, Da(R578H) and Da(A614V) were less potent in induction of ectopic bristles and the rough eye phenotype, respectively, suggesting that these are hypomorphic. All studied PTHS-associated mutations that we introduced into Da led to similar effects in vivo as the same mutations in TCF4 in vitro. Consequently, our Drosophila models of PTHS are applicable for further studies aiming to unravel the molecular mechanisms of this disorder.
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