LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility.

Heterozygous loss of human (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human- induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here, we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from -deficient mutants.

"Females Are Not Just 'Protected' Males": Sex-Specific Vulnerabilities in Placenta and Brain after Prenatal Immune Disruption.

Current perceptions of genetic and environmental vulnerabilities in the developing fetus are biased toward male outcomes. An argument is made that males are more vulnerable to gestational complications and neurodevelopmental disorders, the implication being that an understanding of disrupted development in males is sufficient to understand causal mechanisms that are assumed to be similar but attenuated in females. Here we examine this assumption in the context of immune-driven alterations in fetal brain development and related outcomes in female and male mice.

Stereotypical alterations in cortical patterning are associated with maternal illness-induced placental dysfunction.

We have previously shown in mice that cytokine-mediated damage to the placenta can temporarily limit the flow of nutrients and oxygen to the fetus. The placental vulnerability is pronounced before embryonic day 11, when even mild immune challenge results in fetal loss. As gestation progresses, the placenta becomes increasingly resilient to maternal inflammation, but there is a narrow window in gestation when the placenta is still vulnerable to immune challenge yet resistant enough to allow for fetal survival.

LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein complex.

Heterozygous LIS1 mutations are responsible for the human neuronal migration disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many organisms throughout evolution. However, the cellular functions of LIS1 at distinct intracellular compartments such as the centrosome and the cell cortex have not been well defined especially during mitotic cell division.

Cytoskeleton in action: lissencephaly, a neuronal migration disorder.

During neocortical development, the extensive migratory movements of neurons from their place of birth to their final location are essential for the coordinated wiring of synaptic circuits and proper neurological function. Failure or delay in neuronal migration causes severe abnormalities in cortical layering, which consequently results in human lissencephaly ('smooth brain'), a neuronal migration disorder. The brains of lissencephaly patients have less-convoluted gyri in the cerebral cortex with impaired cortical lamination of neurons.

Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration.

Coordinated migration of newly born neurons to their prospective target laminae is a prerequisite for neural circuit assembly in the developing brain. The evolutionarily conserved LIS1/NDEL1 complex is essential for neuronal migration in the mammalian cerebral cortex. The cytoplasmic nature of LIS1 and NDEL1 proteins suggest that they regulate neuronal migration cell autonomously.

The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection.

Unlabelled: Hepatitis C virus (HCV) is an important cause of chronic liver disease and is complicated by hepatocellular carcinoma (HCC). Mechanisms whereby the virus promotes cellular transformation are poorly understood. We hypothesized that the guanosine triphosphatase activity encoded in the HCV NS4B protein's nucleotide binding motif (NBM) might play a role in the transformation process.

Activated liver X receptors stimulate adipocyte differentiation through induction of peroxisome proliferator-activated receptor gamma expression.

Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro.

Adipocyte determination- and differentiation-dependent factor 1/sterol regulatory element-binding protein 1c regulates mouse adiponectin expression.

Adiponectin is exclusively expressed in differentiated adipocytes and plays an important role in regulating energy homeostasis, including the glucose and lipid metabolism associated with increased insulin sensitivity. However, the control of adiponectin gene expression in adipocytes is poorly understood. We show here that levels of adiponectin mRNA and protein are reduced in the white adipose tissue of ob/ob and db/db mice and that there is a concomitant reduction of the adipocyte determination- and differentiation-dependent factor 1 (ADD1)/sterol regulatory element-binding protein 1c (SREBP1c) transcription factor.