Prenatal Exposure to a Human Relevant Mixture of Endocrine-Disrupting Chemicals Affects Mandibular Development in Mice.

Mandible is a bony structure of neuroectodermal origin with unique characteristics that support dentition and jaw movements. In the present study, we investigated the effects of gestational exposure to a mixture of endocrine-disrupting chemicals (EDCs) on mandibular growth in mice. The mixture under study (Mixture N1) has been associated with neurodevelopmental effects in both a human cohort and animal studies.

Beta-adrenergic stimulation promotes an endoplasmic reticulum stress-dependent inflammatory program in salivary gland epithelial cells.

The effect of beta-adrenergic stimulation on human labial minor salivary gland epithelial cells (LMSGEC) on IL-6 production and its dependency on endoplasmic reticulum (ER) stress were investigated. Primary LMSGEC from Sjögren's syndrome (SS) patients and controls in culture were stimulated with epinephrine and IL-6 expression was evaluated by qPCR and ELISA. The expression of β-ARs in cultured LMSGEC was tested by qPCR, while adrenoceptors and cAMP levels were examined in LMSGs by immunofluorescence.

Nuclear receptor NR5A2 controls neural stem cell fate decisions during development.

The enormous complexity of mammalian central nervous system (CNS) is generated by highly synchronized actions of diverse factors and signalling molecules in neural stem/progenitor cells (NSCs). However, the molecular mechanisms that integrate extrinsic and intrinsic signals to control proliferation versus differentiation decisions of NSCs are not well-understood. Here we identify nuclear receptor NR5A2 as a central node in these regulatory networks and key player in neural development.

Nuclear receptor NR5A2 is involved in the calreticulin gene regulation during renal fibrosis.

Background: Renal fibrosis is a common histological finding present in many pathologies; however, key signaling pathways and molecular determinants involved in the development of fibrosis are not fully known yet. Previous findings have established a causative role of calreticulin's up-regulation during the development of renal fibrosis while its down-regulation exhibited a protective effect against fibrosis. Therefore, the mechanism of its up-regulation needs to be explored.

Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone.

Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG.

Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification.

Over the last decades, adult neurogenesis in the central nervous system (CNS) has emerged as a fundamental process underlying physiology and disease. Recent evidence indicates that the homeobox transcription factor Prox1 is a critical intrinsic regulator of neurogenesis in the embryonic CNS and adult dentate gyrus (DG) of the hippocampus, acting in multiple ways and instructed by extrinsic cues and intrinsic factors. In the embryonic CNS, Prox1 is mechanistically involved in the regulation of proliferation vs.

Prox1 regulates Olig2 expression to modulate binary fate decisions in spinal cord neurons.

Specification of spinal cord neurons depends on gene regulation networks that impose distinct fates in neural progenitor cells (NPCs). Olig2 is a key transcription factor in these networks by inducing motor neuron (MN) specification and inhibiting interneuron identity. Despite the critical role of Olig2 in nervous system development and cancer progression, the upstream molecular mechanisms that control Olig2 gene transcription are not well understood.

Recent advances in the involvement of long non-coding RNAs in neural stem cell biology and brain pathophysiology.

Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs) with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation.

The role of nuclear receptors in controlling the fine balance between proliferation and differentiation of neural stem cells.

In the central nervous system (CNS) of vertebrates a large variety of cell types are specified from a pool of highly plastic neural stem/progenitor cells (NSCs) via a combined action of extrinsic morphogenetic cues and intrinsic transcriptional regulatory networks. Nuclear receptors and their ligands are key regulators of fate decisions in NSCs during development and adulthood, through their ability to control transcription of downstream genes. In the last few years considerable progress has been made towards the understanding of the actions of nuclear receptors in NSCs as well as elucidating the mechanistic basis for these actions.

Prox1 regulates the notch1-mediated inhibition of neurogenesis.

Activation of Notch1 signaling in neural progenitor cells (NPCs) induces self-renewal and inhibits neurogenesis. Upon neuronal differentiation, NPCs overcome this inhibition, express proneural genes to induce Notch ligands, and activate Notch1 in neighboring NPCs. The molecular mechanism that coordinates Notch1 inactivation with initiation of neurogenesis remains elusive.