scholarly journals Cbln1 regulates axon growth and guidance in multiple neural regions

2021 ◽  
Author(s):  
Sheng-Jian Ji ◽  
Peng Han ◽  
Yuanchu She ◽  
Zhuoxuan Yang ◽  
Mengru Zhuang ◽  
...  
Keyword(s):  
Nervous System ◽  
Axon Guidance ◽  
Neural Development ◽  
System Development ◽  
Axon Growth ◽  
Nervous System Development ◽  
Precise Control ◽  
Commissural Neurons ◽  
Guidance Cues ◽  
Guidance Cue

The accurate construction of neural circuits requires the precise control of axon growth and guidance, which is regulated by multiple growth and guidance cues during early nervous system development. It is generally thought that the growth and guidance cues that control the major steps of axon guidance have been defined. Here, we describe cerebellin-1 (Cbln1) as a novel cue that controls diverse aspects of axon growth and guidance throughout the central nervous system (CNS). Cbln1 has previously been shown to function in late neural development to influence synapse organization. Here we find that Cbln1 has an essential role in early neural development. Cbln1 is expressed on the axons and growth cones of developing commissural neurons and functions in an autocrine manner to promote axon growth. Cbln1 is also expressed in intermediate target tissues and functions as an attractive guidance cue. We find that these functions of Cbln1 are mediated by neurexin-2 (Nrxn2), which functions as the Cbln1 receptor for axon growth and guidance. In addition to the developing spinal cord, we further show that Cbln1 functions in diverse parts of the CNS with major roles in cerebellar parallel fiber growth and retinal ganglion cell axon guidance. Despite the prevailing role of Cbln1 as a synaptic organizer, our study discovers a new and unexpected function for Cbln1 as a general axon growth and guidance cue throughout the nervous system.

scholarly journals Analysis of the ENU-3 protein family in nervous system development in C. elegans.

2021 ◽  
Author(s):  
Roxana O. Florica
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
The Novel ◽  
Intracellular Membrane ◽  
C Elegans ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Dependent Pathway ◽  
Novel Protein

During the development of the nervous system, neurons are guided to their final targets by several well-known guidance cues. In Caenorhabditis elegans the expression of the UNC-6/Netrin guidance cue along the ventral cord attracts axons that express UNC-40, while repulsing axons that express both the UNC-5 and UNC-40 receptors. Lack of both UNC-40 and the novel protein ENU-3 enhanced the ventral guidance defects of the AVM and PVM (Yee et al., 2014). This suggests that ENU-3 functions in an UNC-6 dependent pathway parallel to UNC-40 in controlling migrations towards the ventral nerve cord. Mutations in all proteins of the ENU-3 family also enhance the motor neuron axon outgrowth defects of strains lacking UNC-6 or the UNC-5 receptor, thus they function in a parallel unknown pathway (Yee et al., 2011). Expression analyses in HeLa cells have determined that ENU-3 and one of its paralogs, C38D4.1 localize to the nuclear membrane/ER while another of its paralogs, K01G5.3 is an intracellular membrane-associated protein.

scholarly journals Analysis of the ENU-3 protein family in nervous system development in C. elegans.

2021 ◽  
Author(s):  
Roxana O. Florica
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
The Novel ◽  
Intracellular Membrane ◽  
C Elegans ◽  
Guidance Cues ◽  
Guidance Cue ◽  
Dependent Pathway ◽  
Novel Protein

During the development of the nervous system, neurons are guided to their final targets by several well-known guidance cues. In Caenorhabditis elegans the expression of the UNC-6/Netrin guidance cue along the ventral cord attracts axons that express UNC-40, while repulsing axons that express both the UNC-5 and UNC-40 receptors. Lack of both UNC-40 and the novel protein ENU-3 enhanced the ventral guidance defects of the AVM and PVM (Yee et al., 2014). This suggests that ENU-3 functions in an UNC-6 dependent pathway parallel to UNC-40 in controlling migrations towards the ventral nerve cord. Mutations in all proteins of the ENU-3 family also enhance the motor neuron axon outgrowth defects of strains lacking UNC-6 or the UNC-5 receptor, thus they function in a parallel unknown pathway (Yee et al., 2011). Expression analyses in HeLa cells have determined that ENU-3 and one of its paralogs, C38D4.1 localize to the nuclear membrane/ER while another of its paralogs, K01G5.3 is an intracellular membrane-associated protein.

scholarly journals sli is required for proper morphology and migration of sensory neurons in the Drosophila PNS

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Madison Gonsior ◽  
Afshan Ismat
Keyword(s):  
Nervous System ◽  
Sensory Neurons ◽  
Glial Cells ◽  
System Development ◽  
Nervous System Development ◽  
Final Position ◽  
Neuron Development ◽  
Guidance Cues ◽  
And Migration

Abstract Neurons and glial cells coordinate with each other in many different aspects of nervous system development. Both types of cells are receiving multiple guidance cues to guide the neurons and glial cells to their proper final position. The lateral chordotonal organs (lch5) of the Drosophila peripheral nervous system (PNS) are composed of five sensory neurons surrounded by four different glial cells, scolopale cells, cap cells, attachment cells and ligament cells. During embryogenesis, the lch5 neurons go through a rotation and ventral migration to reach their final position in the lateral region of the abdomen. We show here that the extracellular ligand sli is required for the proper ventral migration and morphology of the lch5 neurons. We further show that mutations in the Sli receptors Robo and Robo2 also display similar defects as loss of sli, suggesting a role for Slit-Robo signaling in lch5 migration and positioning. Additionally, we demonstrate that the scolopale, cap and attachment cells follow the mis-migrated lch5 neurons in sli mutants, while the ventral stretching of the ligament cells seems to be independent of the lch5 neurons. This study sheds light on the role of Slit-Robo signaling in sensory neuron development.

scholarly journals aPKC in neuronal differentiation, maturation and function

2019 ◽  
Vol 3 (3) ◽  
Author(s):  
Sophie M. Hapak ◽  
Carla V. Rothlin ◽  
Sourav Ghosh
Keyword(s):  
Nervous System ◽  
Protein Kinase ◽  
Neural Development ◽  
System Development ◽  
Nervous System Development ◽  
Versus Gene ◽  
Metabolic Functions ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
Neuronal Functions

Abstract The atypical Protein Kinase Cs (aPKCs)—PRKCI, PRKCZ and PKMζ—form a subfamily within the Protein Kinase C (PKC) family. These kinases are expressed in the nervous system, including during its development and in adulthood. One of the aPKCs, PKMζ, appears to be restricted to the nervous system. aPKCs are known to play a role in a variety of cellular responses such as proliferation, differentiation, polarity, migration, survival and key metabolic functions such as glucose uptake, that are critical for nervous system development and function. Therefore, these kinases have garnered a lot of interest in terms of their functional role in the nervous system. Here we review the expression and function of aPKCs in neural development and in neuronal maturation and function. Despite seemingly paradoxical findings with genetic deletion versus gene silencing approaches, we posit that aPKCs are likely candidates for regulating many important neurodevelopmental and neuronal functions, and may be associated with a number of human neuropsychiatric diseases.

Dual function of polysialic acid during zebrafish central nervous system development

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 4949-4958
Author(s):  
Monika Marx ◽  
Urs Rutishauser ◽  
Martin Bastmeyer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Pattern ◽  
System Development ◽  
Polysialic Acid ◽  
Axon Growth ◽  
Nervous System Development ◽  
Dual Function ◽  
Central Nervous System Development ◽  
Posterior Commissure

Polysialic acid (PSA), a carbohydrate epitope attached to the neural cell adhesion molecule, serves as a modulator of axonal interactions during vertebrate nervous system development. We have used PSA-specific antibodies and whole-mount immunocytochemistry to describe the spatiotemporal expression pattern of PSA during zebrafish central nervous system development. PSA is transiently expressed on all cell bodies and, except for the posterior commissure, it is not found on axons. Floorplate cells in the spinal cord and hindbrain strongly express PSA throughout development. Enzymatic removal of PSA leads to a defasciculated growth pattern of the posterior commissure and also affects distinct subsets of commissural axons in the hindbrain, which fail to cross the midline. Whereas the disordered growth pattern of hindbrain commissures produced by PSA-removal could be mimicked by injections of soluble PSA, the growth of axons in the posterior commissure was unaffected by such treatment. These results suggest that there are distinct mechanisms for PSA action during axon growth and pathfinding in the developing zebrafish CNS.

Genes required for axon pathfinding and extension in the C. elegans nerve ring

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3679-3692 ◽  
Author(s):  
J.A. Zallen ◽  
S.A. Kirch ◽  
C.I. Bargmann
Keyword(s):  
Axon Guidance ◽  
Fluorescent Protein ◽  
System Development ◽  
Axon Growth ◽  
Ring Structure ◽  
Nervous System Development ◽  
Nerve Ring ◽  
Eph Receptor ◽  
Axon Extension ◽  
Growth Guidance

Over half of the neurons in Caenorhabditis elegans send axons to the nerve ring, a large neuropil in the head of the animal. Genetic screens in animals that express the green fluorescent protein in a subset of sensory neurons identified eight new sax genes that affect the morphology of nerve ring axons. sax-3/robo mutations disrupt axon guidance in the nerve ring, while sax-5, sax-9 and unc-44 disrupt both axon guidance and axon extension. Axon extension and guidance proceed normally in sax-1, sax-2, sax-6, sax-7 and sax-8 mutants, but these animals exhibit later defects in the maintenance of nerve ring structure. The functions of existing guidance genes in nerve ring development were also examined, revealing that SAX-3/Robo acts in parallel to the VAB-1/Eph receptor and the UNC-6/netrin, UNC-40/DCC guidance systems for ventral guidance of axons in the amphid commissure, a major route of axon entry into the nerve ring. In addition, SAX-3/Robo and the VAB-1/Eph receptor both function to prevent aberrant axon crossing at the ventral midline. Together, these genes define pathways required for axon growth, guidance and maintenance during nervous system development.

scholarly journals ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

2020 ◽  
Vol 10 (6) ◽  
pp. 1949-1962 ◽  
Author(s):  
Elyse L. Christensen ◽  
Alexandra Beasley ◽  
Jessica Radchuk ◽  
Zachery E. Mielko ◽  
Elicia Preston ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Neural Development ◽  
System Development ◽  
Neuronal Cell ◽  
Nervous System Development ◽  
Link Type ◽  
Neuroblast Migration

Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.

scholarly journals Unraveling Axon Guidance during Axotomy and Regeneration

2021 ◽  
Vol 22 (15) ◽  
pp. 8344
Author(s):  
Miguel E. Domínguez-Romero ◽  
Paula G. Slater
Keyword(s):  
Nervous System ◽  
Growth Cone ◽  
Neuronal Development ◽  
System Development ◽  
Nervous System Development ◽  
Signaling Cascades ◽  
Final Destination ◽  
Guidance Cues ◽  
The Central Nervous System ◽  
Do So

During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final destination. The guidance cues “signals” bind their receptors, activating signaling cascades that result in the regulation of the growth cone cytoskeleton, defining growth cone advance, pausing, turning, or collapse. Even though much is known about guidance cues and their isolated mechanisms during nervous system development, there is still a gap in the understanding of the crosstalk between them, and about what happens after nervous system injuries. After neuronal injuries in mammals, only axons in the peripheral nervous system are able to regenerate, while the ones from the central nervous system fail to do so. Therefore, untangling the guidance cues mechanisms, as well as their behavior and characterization after axotomy and regeneration, are of special interest for understanding and treating neuronal injuries. In this review, we present findings on growth cone guidance and canonical guidance cues mechanisms, followed by a description and comparison of growth cone pathfinding mechanisms after axotomy, in regenerative and non-regenerative animal models.

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:

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