Goldberg-Shprintzen syndrome protein KIF1BP is a CITK interactor implicated in cytokinesis.

Goldberg-Shprintzen disease (GOSHS) is a rare microcephaly syndrome accompanied by intellectual disability, dysmorphic facial features, peripheral neuropathy and Hirschsprung disease. It is associated with recessive mutations in the gene encoding kinesin family member 1-binding protein (KIF1BP, also known as KIFBP). The encoded protein regulates axon microtubules dynamics, kinesin attachment and mitochondrial biogenesis, but it is not clear how its loss could lead to microcephaly.

miR-7b-3p Exerts a Dual Role After Spinal Cord Injury, by Supporting Plasticity and Neuroprotection at Cortical Level.

Spinal cord injury (SCI) affects 6 million people worldwide with no available treatment. Despite research advances, the inherent poor regeneration potential of the central nervous system remains a major hurdle. Small RNAs (sRNAs) 19-33 nucleotides in length are a set of non-coding RNA molecules that regulate gene expression and have emerged as key players in regulating cellular events occurring after SCI.

CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents.

Medulloblastoma (MB) is the most common malignant brain tumor in children, and it is classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. The current treatment is surgery, followed by irradiation and chemotherapy. Unfortunately, these therapies are only partially effective.

Neuronal Cell-Intrinsic Defects in Mouse Models of Down Syndrome.

Down Syndrome (DS) is the most common genetic disorder associated with intellectual disability (ID). Excitatory neurons of DS patients and mouse models show decreased size of dendritic field and reduction of spine density. Whether these defects are caused by cell autonomous alterations or by abnormal multicellular circuitry is still unknown.

Precision Revisited: Targeting Microcephaly Kinases in Brain Tumors.

Glioblastoma multiforme and medulloblastoma are the most frequent high-grade brain tumors in adults and children, respectively. Standard therapies for these cancers are mainly based on surgical resection, radiotherapy, and chemotherapy. However, intrinsic or acquired resistance to treatment occurs almost invariably in the first case, and side effects are unacceptable in the second.

Correction to: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.

The authors wish to point out that the name of the first author is appearing incorrectly on Pubmed: it should be El Ghouzzi V (and not Ghouzzi VE). In addition, the words "and p53" appear at the end of the title in the original publication ( https://www.nature.

Impact of DNA repair and stability defects on cortical development.

Maintenance of genome stability is a crucial cellular function for normal mammalian development and physiology. However, despite the general relevance of this process, genome stability alteration due to genetic or non-genetic conditions has a particularly profound impact on the developing cerebral cortex. In this review, we will analyze the main pathways involved in maintenance of genome stability, the consequences of their alterations with regard to central nervous system development, as well as the possible molecular and cellular basis of this specificity.

Inactivation of Citron Kinase Inhibits Medulloblastoma Progression by Inducing Apoptosis and Cell Senescence.

Medulloblastoma is the most common malignant brain tumor in children. Current treatment for medulloblastoma consists of surgery followed by irradiation of the whole neuraxis and high-dose multiagent chemotherapy, a partially effective strategy associated with highly invalidating side effects. Therefore, identification and validation of novel target molecules capable of contrasting medulloblastoma growth without disturbing brain development is needed.

Citron kinase-dependent F-actin maintenance at midbody secondary ingression sites mediates abscission.

Abscission is the final step of cytokinesis whereby the intercellular bridge (ICB) linking the two daughter cells is cut. The ICB contains a structure called the midbody, required for the recruitment and organization of the abscission machinery. Final midbody severing is mediated by formation of secondary midbody ingression sites, where the ESCRT III component CHMP4B is recruited to mediate membrane fusion.

Of rings and spines: The multiple facets of Citron proteins in neural development.

The Citron protein was originally identified for its capability to specifically bind the active form of RhoA small GTPase, leading to the simplistic hypothesis that it may work as a RhoA downstream effector in actin remodeling. More than two decades later, a much more complex picture has emerged. In particular, it has become clear that in animals, and especially in mammals, the functions of the Citron gene () are intimately linked to many aspects of central nervous system (CNS) development and function, although the gene is broadly expressed.

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.

[Image: see text]

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly.

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions.

ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly.

Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV and microcephaly. ZIKV infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. However, the mechanisms leading to these phenotypes are still largely obscure.

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.

Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation.

The DCR protein TTC3 affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways.

In neuronal cells, actin remodeling plays a well known role in neurite extension but is also deeply involved in the organization of intracellular structures, such as the Golgi apparatus. However, it is still not very clear which mechanisms may regulate actin dynamics at the different sites. In this report we show that high levels of the TTC3 protein, encoded by one of the genes of the Down Syndrome Critical Region (DCR), prevent neurite extension and disrupt Golgi compactness in differentiating primary neurons.