Topic: Lis1

Approximately 25% of all cortical neurons are inhibitory interneurons, with somatostatin-positive interneurons (SST+ interneurons) representing a distinct subtype expressing both somatostatin and GABA. These cells form synapses with pyramidal neurons and other interneurons, crucial for modulating cortical information processing and maintaining excitation/inhibition balance. Originating from the medial ganglionic eminence, SST+ interneurons follow a tangential pathway to the cortex, making them susceptible to gene mutations affecting neuronal migration. One such gene, Platelet-activating factor

Numerous brain pathologies are characterized by an imbalance between excitatory and inhibitory actions in brain microcircuits. The loss or loss of function of parvalbumin-positive interneurons (PV+), an interneurons subtype, is accompanied by network disturbance and cognitive dysfunction in many neuro-psychiatric diseases. Platelet-activating factor acetylhydrolase 1B subunit alpha (known as Lis1) is a regulator of dynein mediated motility, mitosis nuclear positioning and microtubule organization. Lis1 gene mutation has been associated with lissencephaly in humans and defects in neural migrati

The development of the cerebral cortex involves a series of dynamic events, including cell proliferation and migration, which rely on the motor protein dynein and its regulators NDE1 and NDEL1. While the loss of function in NDE1 leads to microcephaly-related malformations of cortical development (MCDs), NDEL1 variants have not been detected in MCD patients. Here, we identified two patients with pachygyria, with or without subcortical band heterotopia (SBH), carrying the same de novo somatic mosaic NDEL1 variant, p.Arg105Pro (p.R105P). Through single-cell RNA sequencing and spatial transcriptom