Nde1, also known as Nuclear Distribution Element 1 or NudE, is a crucial scaffold protein. It is essential for brain development and is involved in the cytoplasmic dynein-1 pathway, which has functions ranging from cargo trafficking to mitotic spindle formation [1,2,3,4,5,6,7,8,9,10]. Nde1 is associated with multiple biological processes such as neurogenesis, heterochromatin compaction, and intracellular transport of membranous organelles [1,2,3,5,7]. Genetic models, like gene-knockout models, have been valuable in studying its 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 such as increased locomotor activity, repetitive stereotype behaviors, and impaired social and kin recognition behaviors. This indicates that nde1 homozygous deletion causes abnormal neurological development with autism-related behavioral phenotypes, suggesting that Nde1 plays a key role in normal neurological development [9]. In mice, 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, uncovering its pivotal role in establishing and protecting neuronal heterochromatin [5].

In conclusion, Nde1 is essential for brain development, participating in key biological processes like neurogenesis and heterochromatin regulation. The study of Nde1 using gene-knockout models, such as in zebrafish and mice, has provided insights into its role in neurological development and disorders, especially in relation to autism-like behaviors and microcephaly, contributing to our understanding of the underlying mechanisms of these conditions [5,9].