Developmental Neurobiology最新文献

Axon pruning facilitates the removal of ectopic and misguided axons and plays an important role in neural circuit formation during brain development. Sema3F and its receptor neuropilin-2 (Nrp2) have been shown to be involved in the stereotyped pruning of the infrapyramidal bundle (IPB) of mossy fibers of the dentate gyrus (DG) in the developing hippocampus.

Collapsin response mediator proteins (CRMPs) were originally identified as an intracellular mediator of semaphorin signaling, and the defective pruning of IPB was recently reported in CRMP2-/- and CRMP3-/- mice. CRMP1 and CRMP4 have high homology to CRMP2 and CRMP3, and their expression in the developing mouse brain overlaps; however, their role in IPB pruning has not yet been examined.

In this study, we report that CRMP4, but not CRMP1, is involved in IPB pruning during neural circuit formation in the hippocampus. Our genetic interaction analyses indicated that CRMP2 and CRMP4 have distinct functions and that CRMP2 mediates IPB pruning via Nrp2. We also observed the altered synaptic terminals of mossy fibers in CRMP2 and CRMP4 mutant mice. These results suggest that CRMP family members have a distinct function in the axon pruning and targeting of mossy fibers of the hippocampal DG in the developing mouse brain.

Microglia are important immune cells in the central nervous system. There is growing interest in the study of microglia due to their implication in neurodevelopment, acute injury, and neuropsychiatric disorders. They undergo birth, death, and regeneration during the lifetime. Although data on the ontogeny of microglia have been studied for decades, the birth and repopulation of microglia remain legendary and mysterious. In this review, we discuss recent studies that provide new insights into the origin and regeneration of microglia. Modulating the development of microglia may offer new therapeutic opportunities for preventing deleterious effects of inflammation and controlling excessive inflammation in brain diseases.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an aggressive motor neuron degenerative disease characterized by selective loss of both upper and lower motor neurons. The mechanisms underlying disease initiation and progression are poorly understood. The involvement of nonmotor neuraxis emphasizes the contribution of glial cells in disease progress. Microglia comprise a unique subset of glial cells and are the principal immune cells in the central nervous system (CNS). Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, within the CNS, is exclusively expressed on microglia and plays crucial roles in microglial proliferation, migration, activation, metabolism, and phagocytosis. Genetic evidence has linked TREM2 to neurodegenerative diseases including ALS, but its function in ALS pathogenesis is largely unknown. In this review, we summarize how microglial activation, with a specific focus on TREM2 function, affects ALS progression clinically and experimentally. Understanding microglial TREM2 function will help pinpoint the molecular target for ALS treatment.

Hundreds of millions of people worldwide suffer from peripheral nerve damage resulting from car accidents, falls, industrial accidents, residential accidents, and wars. The purpose of our study was to further investigate the effects of Wallerian degeneration (WD) after rat sciatic nerve injury and to screen for critical long noncoding RNAs (lncRNAs) in WD. We found H19 to be essential for nerve degeneration and regeneration and to be highly expressed in the sciatic nerves of rats with WD. lncRNA H19 potentially impaired the recovery of sciatic nerve function in rats. H19 was mainly localized in the cytoplasm of Schwann cells (SCs) and promoted their migration. H19 promoted the apoptosis of dorsal root ganglion (DRG) neurons and slowed the growth of DRG axons. The lncRNA H19 may play a role in WD through the Wnt/β-catenin signaling pathway and is coexpressed with a variety of crucial mRNAs during WD. These data provide further insight into the molecular mechanisms of WD.

Interferon regulatory factor-7 (IRF7) is an essential regulator of both innate and adaptive immunity. It is also expressed in the otic vesicle of zebrafish embryos. However, any role for irf7 in hair cell development was uncharacterized. Does it work as a potential deaf gene to regulate hair cell development? We used whole-mount in situ hybridization (WISH) assay and morpholino-mediated gene knockdown method to investigate the role of irf7 in the development of otic vesicle hair cells during zebrafish embryogenesis. We performed RNA sequencing to gain a detailed insight into the molecules/genes which are altered upon downregulation of irf7. Compared to the wild-type siblings, knockdown of irf7 resulted in severe developmental retardation in zebrafish embryos as well as loss of neuromasts and damage to hair cells at an early stage (within 3 days post fertilization). Coinjection of zebrafish irf7 mRNA could partially rescued the defects of the morphants. atp1b2b mRNA injection can also partially rescue the phenotype induced by irf7 gene deficiency. Loss of hair cells in irf7-morphants does not result from cell apoptosis. Gene expression profiles show that, compared to wild-type, knockdown of irf7 can lead to 2053 and 2678 genes being upregulated and downregulated, respectively. Among them, 18 genes were annotated to hair cell (HC) development or posterior lateral line (PLL) development. All results suggest that irf7 plays an essential role in hair cell development in zebrafish, indicating that irf7 may be a member of deafness gene family.

Mammalian TRPC5 channels are predominantly expressed in the brain, where they increase intracellular Ca²⁺ and induce depolarization. Because they augment presynaptic vesicle release, cause persistent neural activity, and show constitutive activity, TRPC5s could play a functional role in late developmental brain events. We used immunohistochemistry to examine TRPC5 in the chick embryo brain between 8 and 20 days of incubation, and provide the first detailed description of their distribution in birds and in the whole brain of any animal species. Stained areas substantially increased between E8 and E16, and staining intensity in many areas peaked at E16, a time when chick brains first show organized patterns of whole-brain metabolic activation like what is seen consistently after hatching. Areas showing cell soma staining match areas showing Trpc5 mRNA or protein in adult rodents (cerebral cortex, hippocampus, amygdala, cerebellar Purkinje cells). Chick embryos show protein staining in the optic tectum, cerebellar nuclei, and several brainstem nuclei; equivalent areas in the Allen Institute mouse maps express Trpc5 mRNA. The strongest cell soma staining was found in a dorsal hypothalamic area (matching a group of parvicellular arginine vasotocin neurons and a pallial amygdalohypothalamic cell corridor) and the vagal motor complex. Purkinje cells showed strong dendritic staining at E20. Unexpectedly, we also describe neurite staining in the septum, several hypothalamic nuclei, and a paramedian raphe area; the strongest neurite staining was in the median eminence. These novel localizations suggest new unexplored TRPC5 functions, and possible roles in late embryonic brain development.

The harmful consumption of ethanol is associated with significant health problems and social burdens. This drug activates a complex network of reward mechanisms and habit formation learning that is supposed to contribute to the consumption of increasingly high and frequent amounts, ultimately leading to addiction. In the context of fetal alcohol spectrum disorders, fetal alcohol syndrome (FAS) is a consequence of the harmful use of alcohol during pregnancy, which affects the embryonic development of the fetus. FAS can be easily reproduced in zebrafish by exposing the embryos to different concentrations of ethanol in water. In this regard, the aim of the present review is to discuss the late pathological implications in zebrafish exposed to ethanol at the embryonic stage, providing information in the context of human fetal alcoholic spectrum disorders. Experimental FAS in zebrafish is associated with impairments in the metabolic, morphological, neurochemical, behavioral, and cognitive domains. Many of the pathways that are affected by ethanol in zebrafish have at least one ortholog in humans, collaborating with the wider adoption of zebrafish in studies on alcohol disorders. In fact, zebrafish present validities required for the study of these conditions, which contributes to the use of this species in research, in addition to studies with rodents.

The fate of neurons in the developing brain is largely determined by the combination of transcription factors they express. In particular, stem cells must follow different transcriptional cascades during differentiation in order to generate neurons with different neurotransmitter properties, such as glutamatergic and GABAergic neurons. In the mouse cerebral cortex, it has been shown that large Maf family proteins, MafA, MafB and c-Maf, regulate the development of specific types of GABAergic interneurons but are not expressed in glutamatergic neurons. In this study, we examined the expression of large Maf family proteins in the developing mouse olfactory bulb (OB) by immunohistochemistry and found that the cell populations expressing MafA and MafB are almost identical, and most of them express Tbr2. As Tbr2 is expressed in glutamatergic neurons in the OB, we further examined the expression of glutamatergic and GABAergic neuronal markers in MafA and MafB positive cells. The results showed that in the OB, MafA and MafB are expressed exclusively in glutamatergic neurons, but not in GABAergic neurons. We also found that few cells express c-Maf in the OB. These results indicate that, unlike the cerebral cortex, MafA and/or MafB may regulate the development of glutamatergic neurons in the developing OB. This study advances our knowledge about the development of glutamatergic neurons in the olfactory bulb, and also might suggest that mechanisms for the generation of projection neurons and interneurons differ between the cortex and the olfactory bulb, even though they both develop from the telencephalon.

In the field of face processing, the so-called “core network” has been intensively researched. Its neural activity can be reliably detected in children and adults using functional magnetic resonance imaging (fMRI). However, the core network's counterpart, the so-called “extended network,” has been less researched. In the present study, we compared children's and adults’ brain activity in the extended system, in particular in the amygdala, the insula, and the inferior frontal gyrus (IFG). Using fMRI, we compared the brain activation pattern between children aged 7–9 years and adults during an emotional face processing task. On the one hand, children showed increased activity in the extended face processing system in relation to adults, particularly in the left amygdala, the right insula, and the left IFG. On the other hand, lateralization indices revealed a “leftward bias” in children's IFG compared to adults. These results suggest that brain activity associated with face processing is characterized by a developmental decrease in activity. They further show that the development is associated with a rightward migration of face-related IFG activation, possibly due to the competition for neural space between several developing brain functions (“developmental competition hypothesis”).

Oligodendrocytes, the myelinating cells of the central nervous system (CNS), develop from oligodendrocyte progenitor cells (OPCs) that must first migrate extensively throughout the developing brain and spinal cord. Specified at particular times from discrete regions in the developing CNS, OPCs are one of the most migratory of cell types and disperse rapidly. A variety of factors act on OPCs to trigger intracellular changes that regulate their migration. We will discuss factors that act as long-range guidance cues, those that act to regulate cellular motility, and those that are critical in determining the final positioning of OPCs. In addition, recent evidence has identified the vasculature as the physical substrate used by OPCs for their migration. Several new findings relating to this oligodendroglial–vascular signaling axis reveal new insight on the relationship between OPCs and blood vessels in the developing and adult brain.