Topic: lissencephaly

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

Development of the cerebral cortex involves many phases, including neural stem cell proliferation, neuronal migration, and differentiation. Defects in these phases lead to malformations in cortical development (MCDs). For example, disruption in neuronal migration causes lissencephaly, a form of MCD characterized by a smooth brain surface. Mutations in a number of genes, such as PAFAH1B1 (aka LIS1), DCX, TUBA1A, ARX, and DYNC1H1, are common causes behind lissencephaly. Many of those genes are involved in microtubule assembly and stabilization during neuronal migration. Recently, mutations in MA

Pathogenic variants in DCX on the X chromosome lead to lissencephaly and subcortical band heterotopia (SBH), brain malformations caused by neuronal migration defects. Doublecortin (DCX) binds to microtubules to modulate microtubule polymerization. How pathogenic DCX variants affect these activities remains not fully investigated. Our aim is to examine whether these variants affect microtubule binding and dynamics and develop a verification tool to apply on clinical research. DCX variants were identified using whole exome and Sanger sequencing from six families with lissencephaly/SBH. We examin

The transcription factor P73 belongs to the p53 protein family, and its gene encodes two main isoforms: the transcriptionally active TAp73 isoform and the dominant-negative ΔNp73. Both isoforms play pivotal roles in regulating the self-renewal and differentiation of neural stem/progenitor cells, thus play a critical role in brain development during neuronal differentiation. Mutations in TP73 are associated with lissencephaly in humans and severe brain defects in mice. The role of TP73 and its isoforms during neurogenesis in human is still unclear. Aiming to further scrutinize the role of TAP73

LIN28A is an RNA-binding protein and stem cell marker, and its overexpression was described in rare malignant brain tumours of early childhood. CTNNB1 is an effector of the WNT pathway which plays important roles during development and activating mutations have been reported in malignant brain tumours. In order to investigate the interplay of these oncogenic proteins during embryonal brain development, we overexpressed both in murine neural progenitor cells in vivo.The sole overexpression of either LIN28A, stabilized Ctnnb1 or the combination of both in hGFAP-positive forebrain precursor cells