ADNP, also known as Activity Dependent Neuroprotective Protein, is crucial for mammalian brain formation [4]. It is associated with chromatin remodeling, interacting with proteins like HP1, BRG1, and in murine stem cells, with CHD4 in a ChAHP complex [3]. Additionally, ADNP is involved in the autophagy pathway [4].

ADNP haploinsufficiency in mice causes cognitive and social deficits, as well as tauopathy-like features including increased formation of tangle-like structures, defective axonal transport, and Tau hyperphosphorylation [5]. In zebrafish, adnp gene disruption leads to defective neurogenesis and reduced Wnt signaling [1]. In humans, heterozygous and predicted loss-of-function ADNP mutations result in Helsmoortel-Van der Aa syndrome, a form of syndromic autism with features such as intellectual disability, autism, speech and motor delay [2,3].

In conclusion, ADNP is essential for neural development and normal cognitive function. Studies on gene-knockout models, like in mice and zebrafish, have revealed its role in neural induction, differentiation, and in the context of neurodevelopmental disorders such as autism and Helsmoortel-Van der Aa syndrome. These models have provided valuable insights into the molecular mechanisms underlying these diseases.

References:

1. Sun, Xiaoyun, Peng, Xixia, Cao, Yuqin, Zhou, Yan, Sun, Yuhua. 2020. ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling. In Nature communications, 11, 2984. doi:10.1038/s41467-020-16799-0. https://pubmed.ncbi.nlm.nih.gov/32533114/

2. Van Dijck, Anke, Vulto-van Silfhout, Anneke T, Cappuyns, Elisa, Vandeweyer, Geert, Kooy, R Frank. 2018. Clinical Presentation of a Complex Neurodevelopmental Disorder Caused by Mutations in ADNP. In Biological psychiatry, 85, 287-297. doi:10.1016/j.biopsych.2018.02.1173. https://pubmed.ncbi.nlm.nih.gov/29724491/

3. D'Incal, Claudio Peter, Van Rossem, Kirsten Esther, De Man, Kevin, Vanden Berghe, Wim, Kooy, R Frank. 2023. Chromatin remodeler Activity-Dependent Neuroprotective Protein (ADNP) contributes to syndromic autism. In Clinical epigenetics, 15, 45. doi:10.1186/s13148-023-01450-8. https://pubmed.ncbi.nlm.nih.gov/36945042/

4. Sragovich, Shlomo, Merenlender-Wagner, Avia, Gozes, Illana. 2017. ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease. In BioEssays : news and reviews in molecular, cellular and developmental biology, 39, . doi:10.1002/bies.201700054. https://pubmed.ncbi.nlm.nih.gov/28940660/

5. Ivashko-Pachima, Yanina, Gozes, Illana. 2020. Activity-dependent neuroprotective protein (ADNP)-end-binding protein (EB) interactions regulate microtubule dynamics toward protection against tauopathy. In Progress in molecular biology and translational science, 177, 65-90. doi:10.1016/bs.pmbts.2020.07.008. https://pubmed.ncbi.nlm.nih.gov/33453943/