Nde1, also known as Nuclear Distribution Element 1 or NudE, is a scaffold protein essential for multiple biological processes. It is intricately involved in the dynein-mediated transport pathway, where cytoplasmic dynein-1, a key microtubule minus-end directed molecular motor, relies on Nde1 and other regulatory proteins to interact with cargo and move along microtubules [1]. Nde1 is also crucial for brain development, with its aberrations linked to neuropsychiatric disorders and congenital microcephaly [2,3]. Genetic models, such as knockout (KO) mouse models, are valuable for studying Nde1's functions.

In zebrafish, nde1 homologous deficiency (nde1 -/-) leads to increased neurological apoptotic responses in early infancy, enlarged ventricles, and shrank valvula cerebelli in adult brain tissue. Behaviorally, nde1 -/- zebrafish display autism-like traits including increased locomotor activity, repetitive stereotype behaviors, and impaired social and kin recognition behaviors [4]. In mouse models, Nde1 is required for heterochromatin compaction and stability in neocortical neurons. Nde1 loss-of-function (LOF) results in nuclear architecture aberrations, DNA double-strand breaks, and instability and derepression of pericentromeric satellite repeats [2].

In conclusion, Nde1 plays essential roles in dynein-mediated transport and brain development. Studies using KO models in zebrafish and mice have revealed its significance in neurodevelopmental processes and the manifestation of neuropsychiatric disorders, highlighting its potential as a key target for understanding and treating related diseases.

References:

1. Garrott, Sharon R, Gillies, John P, DeSantis, Morgan E. 2022. Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport. In Frontiers in cell and developmental biology, 10, 871935. doi:10.3389/fcell.2022.871935. https://pubmed.ncbi.nlm.nih.gov/35493069/

2. Chomiak, Alison A, Guo, Yan, Kopsidas, Caroline A, Doughty, Martin L, Feng, Yuanyi. 2022. Nde1 is required for heterochromatin compaction and stability in neocortical neurons. In iScience, 25, 104354. doi:10.1016/j.isci.2022.104354. https://pubmed.ncbi.nlm.nih.gov/35601919/

3. Soto-Perez, Jaseph, Baumgartner, Marybeth, Kanadia, Rahul N. 2020. Role of NDE1 in the Development and Evolution of the Gyrified Cortex. In Frontiers in neuroscience, 14, 617513. doi:10.3389/fnins.2020.617513. https://pubmed.ncbi.nlm.nih.gov/33390896/

4. Zhang, Qi, Li, Tingting, Lin, Jia, Wang, Xu, Li, Qiang. 2022. Deficiency of nde1 in zebrafish induces brain inflammatory responses and autism-like behavior. In iScience, 25, 103876. doi:10.1016/j.isci.2022.103876. https://pubmed.ncbi.nlm.nih.gov/35243238/