scholarly journals Conservation and Innovation: Versatile Roles for LRP4 in Nervous System Development

2021 ◽  
Vol 9 (1) ◽  
pp. 9
Author(s):  
Alison T. DePew ◽  
Timothy J. Mosca
Keyword(s):  
Nervous System ◽  
Cell Surface ◽  
Current Knowledge ◽  
System Development ◽  
Critical Role ◽  
Surface Protein ◽  
Nervous System Development ◽  
Cell Surface Receptor ◽  
Synaptic Development ◽  
Disease Etiology

As the nervous system develops, connections between neurons must form to enable efficient communication. This complex process of synaptic development requires the coordination of a series of intricate mechanisms between partner neurons to ensure pre- and postsynaptic differentiation. Many of these mechanisms employ transsynaptic signaling via essential secreted factors and cell surface receptors to promote each step of synaptic development. One such cell surface receptor, LRP4, has emerged as a synaptic organizer, playing a critical role in conveying extracellular signals to initiate diverse intracellular events during development. To date, LRP4 is largely known for its role in development of the mammalian neuromuscular junction, where it functions as a receptor for the synaptogenic signal Agrin to regulate synapse development. Recently however, LRP4 has emerged as a synapse organizer in the brain, where new functions for the protein continue to arise, adding further complexity to its already versatile roles. Additional findings indicate that LRP4 plays a role in disorders of the nervous system, including myasthenia gravis, amyotrophic lateral sclerosis, and Alzheimer’s disease, demonstrating the need for further study to understand disease etiology. This review will highlight our current knowledge of how LRP4 functions in the nervous system, focusing on the diverse developmental roles and different modes this essential cell surface protein uses to ensure the formation of robust synaptic connections.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

scholarly journals Interaction Between the Complement System and Infectious Agents – A Potential Mechanistic Link to Neurodegeneration and Dementia

2021 ◽  
Vol 15 ◽  
Author(s):  
Noriko Shinjyo ◽  
Wataru Kagaya ◽  
Marcela Pekna
Keyword(s):  
Nervous System ◽  
Complement System ◽  
Complement Activation ◽  
Neural Plasticity ◽  
Measles Virus ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Infectious Agents ◽  
The Complement System

As part of the innate immune system, complement plays a critical role in the elimination of pathogens and mobilization of cellular immune responses. In the central nervous system (CNS), many complement proteins are locally produced and regulate nervous system development and physiological processes such as neural plasticity. However, aberrant complement activation has been implicated in neurodegeneration, including Alzheimer’s disease. There is a growing list of pathogens that have been shown to interact with the complement system in the brain but the short- and long-term consequences of infection-induced complement activation for neuronal functioning are largely elusive. Available evidence suggests that the infection-induced complement activation could be protective or harmful, depending on the context. Here we summarize how various infectious agents, including bacteria (e.g., Streptococcus spp.), viruses (e.g., HIV and measles virus), fungi (e.g., Candida spp.), parasites (e.g., Toxoplasma gondii and Plasmodium spp.), and prion proteins activate and manipulate the complement system in the CNS. We also discuss the potential mechanisms by which the interaction between the infectious agents and the complement system can play a role in neurodegeneration and dementia.

scholarly journals SOX Transcription Factors as Important Regulators of Neuronal and Glial Differentiation During Nervous System Development and Adult Neurogenesis

2021 ◽  
Vol 14 ◽  
Author(s):  
Milena Stevanovic ◽  
Danijela Drakulic ◽  
Andrijana Lazic ◽  
Danijela Stanisavljevic Ninkovic ◽  
Marija Schwirtlich ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Adult Neurogenesis ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Glial Differentiation ◽  
Neural Lineage ◽  
Stage Of Development ◽  
Sox Proteins

The SOX proteins belong to the superfamily of transcription factors (TFs) that display properties of both classical TFs and architectural components of chromatin. Since the cloning of the Sox/SOX genes, remarkable progress has been made in illuminating their roles as key players in the regulation of multiple developmental and physiological processes. SOX TFs govern diverse cellular processes during development, such as maintaining the pluripotency of stem cells, cell proliferation, cell fate decisions/germ layer formation as well as terminal cell differentiation into tissues and organs. However, their roles are not limited to development since SOX proteins influence survival, regeneration, cell death and control homeostasis in adult tissues. This review summarized current knowledge of the roles of SOX proteins in control of central nervous system development. Some SOX TFs suspend neural progenitors in proliferative, stem-like state and prevent their differentiation. SOX proteins function as pioneer factors that occupy silenced target genes and keep them in a poised state for activation at subsequent stages of differentiation. At appropriate stage of development, SOX members that maintain stemness are down-regulated in cells that are competent to differentiate, while other SOX members take over their functions and govern the process of differentiation. Distinct SOX members determine down-stream processes of neuronal and glial differentiation. Thus, sequentially acting SOX TFs orchestrate neural lineage development defining neuronal and glial phenotypes. In line with their crucial roles in the nervous system development, deregulation of specific SOX proteins activities is associated with neurodevelopmental disorders (NDDs). The overview of the current knowledge about the link between SOX gene variants and NDDs is presented. We outline the roles of SOX TFs in adult neurogenesis and brain homeostasis and discuss whether impaired adult neurogenesis, detected in neurodegenerative diseases, could be associated with deregulation of SOX proteins activities. We present the current data regarding the interaction between SOX proteins and signaling pathways and microRNAs that play roles in nervous system development. Finally, future research directions that will improve the knowledge about distinct and various roles of SOX TFs in health and diseases are presented and discussed.

scholarly journals The Role of Chondroitin Sulfate Proteoglycans in Nervous System Development

2020 ◽  
Vol 69 (1) ◽  
pp. 61-80 ◽  
Author(s):  
Caitlin P. Mencio ◽  
Rowan K. Hussein ◽  
Panpan Yu ◽  
Herbert M. Geller
Keyword(s):  
Nervous System ◽  
Chondroitin Sulfate ◽  
Neural Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Chondroitin Sulfate Proteoglycans ◽  
Cell Proliferation And Differentiation

The orderly development of the nervous system is characterized by phases of cell proliferation and differentiation, neural migration, axonal outgrowth and synapse formation, and stabilization. Each of these processes is a result of the modulation of genetic programs by extracellular cues. In particular, chondroitin sulfate proteoglycans (CSPGs) have been found to be involved in almost every aspect of this well-orchestrated yet delicate process. The evidence of their involvement is complex, often contradictory, and lacking in mechanistic clarity; however, it remains obvious that CSPGs are key cogs in building a functional brain. This review focuses on current knowledge of the role of CSPGs in each of the major stages of neural development with emphasis on areas requiring further investigation:

scholarly journals The role of astrocyte‐mediated plasticity in neural circuit development and function

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Nelson A. Perez-Catalan ◽  
Chris Q. Doe ◽  
Sarah D. Ackerman
Keyword(s):  
Nervous System ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Functional Changes ◽  
Sensory Evoked ◽  
And Function

AbstractNeuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.

scholarly journals Deficiency of Pro-apoptotic Hrk Attenuates Programmed Cell Death in the Developing Murine Nervous System but Does Not Affect Bcl-x Deficiency-Induced Neuron Apoptosis

2011 ◽  
Vol 59 (11) ◽  
pp. 976-983 ◽  
Author(s):  
Arindam P. Ghosh ◽  
Jennifer D. Cape ◽  
Barbara J. Klocke ◽  
Kevin A. Roth
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
System Development ◽  
Critical Role ◽  
Family Members ◽  
Nervous System Development ◽  
Neuronal Populations ◽  
Embryonic Nervous System ◽  
Induced Neuron

The BCL-2 family includes both pro- and anti-apoptotic proteins, which regulate programmed cell death during development and in response to various apoptotic stimuli. The BH3-only subgroup of pro-apoptotic BCL-2 family members is critical for the induction of apoptotic signaling, by binding to and neutralizing anti-apoptotic BCL-2 family members. During embryonic development, the anti-apoptotic protein BCL-XL plays a critical role in the survival of neuronal populations by regulating the multi-BH domain protein BAX. In this study, the authors investigated the role of Harakiri (HRK), a relatively recently characterized BH3-only molecule in disrupting the BAX-BCL-XL interaction during nervous system development. Results indicate that HRK deficiency significantly reduces programmed cell death in the nervous system. However, HRK deficiency does not significantly attenuate the widespread apoptosis seen in the Bcl-x−/− embryonic nervous system, indicating that other BH3-only molecules, alone or in combination, may regulate BAX activation in immature neurons.

scholarly journals Phosphotyrosine 1062 Is Critical for the In Vivo Activity of the Ret9 Receptor Tyrosine Kinase Isoform

2005 ◽  
Vol 25 (21) ◽  
pp. 9661-9673 ◽  
Author(s):  
Adrianne Wong ◽  
Silvia Bogni ◽  
Pille Kotka ◽  
Esther de Graaff ◽  
Vivette D'Agati ◽  
...  
Keyword(s):  
Nervous System ◽  
Amino Acid ◽  
Tyrosine Kinase ◽  
Enteric Nervous System ◽  
Receptor Tyrosine Kinase ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Binding Motif

ABSTRACT The receptor tyrosine kinase Ret plays a critical role in the development of the mammalian excretory and enteric nervous systems. Differential splicing of the primary Ret transcript results in the generation of two main isoforms, Ret9 and Ret51, whose C-terminal amino acid tails diverge after tyrosine (Y) 1062. Monoisoformic mice expressing only Ret9 develop normally and are healthy and fertile. In contrast, animals expressing only Ret51 have aganglionosis of the distal gut and hypoplastic kidneys. By generating monoisoformic mice in which Y1062 of Ret9 has been mutated to phenylalanine, we demonstrate that this amino acid has a critical role in Ret9 signaling that is necessary for the development of the kidneys and the enteric nervous system. These findings argue that the distinct activities of Ret9 and Ret51 result from the differential regulation of Y1062 by C-terminal flanking sequences. However, a mutation which places Y1062 of Ret51 in a Ret9 context improves only marginally the ability of Ret51 to support renal and enteric nervous system development. Finally, monoisoformic mice expressing a variant of Ret9 in which a C-terminal PDZ-binding motif was mutated develop normally and are healthy. Our studies identify Y1062 as a critical regulator of Ret9 signaling and suggest that Ret51-specific motifs are likely to inhibit the activity of this isoform.

scholarly journals nor-1 Regulates Hippocampal Axon Guidance, Pyramidal Cell Survival, and Seizure Susceptibility

2004 ◽  
Vol 24 (20) ◽  
pp. 9070-9078 ◽  
Author(s):  
Tiia Pönniö ◽  
Orla M. Conneely
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Axonal Guidance ◽  
Seizure Susceptibility ◽  
Mammalian Development

ABSTRACT The nuclear receptor transcription factor, nor-1, is expressed during mammalian development predominantly in the nervous system and is induced in a cell-specific manner in nonneuronal cells in response to a variety of extracellular stimuli. To elucidate the essential developmental functions of this transcription factor, we have analyzed the consequences of its elimination on central nervous system development in mice. Here we show that null mutant mice lacking nor-1 respond with increased limbic seizure activity to the excitotoxic glutamate receptor agonist kainic acid. We demonstrate that these abnormalities are associated with defective postnatal hippocampal development exemplified by abnormal axonal guidance of dentate gyrus granule and mossy cells, disorganization of the pyramidal cell layer, and early postnatal death of pyramidal neurons in the CA1 field of the hippocampus. Our data indicate that nor-1 plays a critical role in neuronal survival and axonal guidance in the developing murine hippocampus and that hippocampal dysgenesis in nor-1−/− mice may be an underlying cause of seizure susceptibility.

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