The development of early pioneer neurons in the annelid Malacoceros fuliginosus

Abstract Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus . Results Here, we performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 hours postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d 221 ), which after 7 cleavages starts expressing Neurogenin , Achaete-Scute and NeuroD . Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. The specification of the relevant neurons starts very early and we suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

Download Full-text

The development of early pioneer neurons in the annelid Malacoceros fuliginosus

BMC Evolutionary Biology ◽

10.1186/s12862-020-01680-x ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Suman Kumar ◽

Sharat Chandra Tumu ◽

Conrad Helm ◽

Harald Hausen

Keyword(s):

Nervous System ◽

Synapse Formation ◽

System Development ◽

Posterior Pole ◽

Nervous System Development ◽

Whole Body ◽

Neural Patterning ◽

Neuronal Progenitors ◽

Pioneer Neurons ◽

Clonal Origin

Abstract Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

Download Full-text

The neuron pioneering the ventral nerve cord does not follow the common pathway of neurogenesis in the polychaete Malacoceros fuliginosus

10.21203/rs.2.19981/v1 ◽

2020 ◽

Author(s):

Suman Kumar ◽

Sharat Chandra Tumu ◽

Conrad Helm ◽

Harald Hausen

Keyword(s):

Nervous System ◽

Nerve Cord ◽

Ventral Nerve Cord ◽

System Development ◽

Nervous System Development ◽

Whole Body ◽

Hierarchical Level ◽

Major Influence ◽

Extrinsic Factors ◽

Pioneer Neurons

Abstract Background: Nervous system development is an interplay of many processes: the formation of individual neurons which depends on whole-body and local patterning processes and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the early steps of nervous system development in the annelid Malacoceros fuliginosus.Results: We find that the first pioneer neurons are already in place in the anterior and posterior pole when broad neurogenesis is just starting. They do not express serotonin or FMRFamide which are commonly used markers in studies on nervous system architecture. A single posterior neuron prefigures the main course of the ventral nerve cord and this mode is probably ancestral for majority of annelids. Notably, none of the studied sox and proneural genes, which are commonly involved in the generation of neurons, is expressed by this important neuron. The only transcription factor we found expressed is Brn3, which likely acts on a low hierarchical level.Conclusions: We propose that the annelid ventral nerve cord pioneer neuron follows a highly divergent course of neurogenesis. The lack of Sox and proneural transcription factors, which are usually under control of patterning cell-extrinsic factors suggest a major influence of inherited cell-intrinsic properties on the development of this cell. Though cell-autonomous specification is generally an important pathway in the early development of spirally cleaving animals, its relevance for nervous system development is poorly understood. Our data suggest that closer investigation of the specification of pioneer neurons in animals featuring spiral cleavage will be highly informative to obtain a better understanding of how nervous systems form and evolve.

Download Full-text

New data on dinophilid neurogenesis: a variation of a common pattern

10.21203/rs.3.rs-63064/v1 ◽

2020 ◽

Author(s):

Elizaveta Fofanova ◽

Tatiana Mayorova ◽

Elena Voronezhskaya

Keyword(s):

Nervous System ◽

Developmental Stages ◽

System Development ◽

Nervous System Development ◽

Model Systems ◽

Common Pattern ◽

Acetylated Tubulin ◽

Reported Study ◽

Pioneer Neurons ◽

Tubulin Antibodies

Abstract BackgroundThe structure and development of the nervous system in Lophotrochozoa species is of the most important questions for comparative neurobiology. During the last decade the number of comprehensive studies on the development of serotonergic and FMRFamidergic systems has been skyrocketing. However, the detailed research of the earliest events of Polychaeta neurogenesis is still sparce. Polychaeta is a huge taxon within Lophotrochozoa. Its representatives are widely used as model systems in developmental and physiological investigations. Dinophilidae is a unique Polychaeta group. Its representatives combine morphological traits of different lophotrochozoan taxa. Moreover, adult dinophilids demonstrate morphological similarity to a trochophore larva. This similarity may be associated with either archaic origin of this group or neoteny. The main goal of our study is to provide a detailed description of the earliest events in Dinophilus neurogenesis. These data might improve our understanding of Polychaeta development and evolution.ResultsWe have studied the earliest events in nervous system development in two relative species D. gyrociliatus and D. taeniatus using immunochemical labelling of serotonin, FMRF-amide related peptides, and acetylated tubulin. We used external ciliation as marker for staging. Both species go through the same developmental stages: prototroch, ventral ciliary field and ciliary bands. In both species the first neurons differenciate revealed by anti alpha-acetylated tubulin antibodies only and show no reaction with 5-HT or FMRFa antibodies. These neurons located at the anterior and posterior parts of the embryo in both species. In D. taeniatus embryons the anterior cell is transient and disappear just after head neuropil is constructed. On the contrary, in D. gyrociliatus embryos the anterior cell is not transient and remains at the same position during the whole life span of the specimen. Caudal cell is present during the whole embryogenesis in both species. Neurites of these early neurons surround the stomadeum and constitute anlagen of paired ventro-lateral longitudinal bundles. During the development the number of neurites increases and they form compact head neuropil, paired ventro-lateral and lateral longitudinal bundles, unpaired medial longitudinal bundle and transverse commissures in ventral hyposphere. Serotonin- and FMRFamide-immunoreactive neurons differentiate adjacent to ventro-lateral bundles and head neuropil, respectively, after the establishment of main structures of the nervous system at the ventral ciliary field and ciliary bands stages. Processes of serotonin-, FMRFamide- immunopositive neurons constitute the small portion of tubulin immunopositive neuropil at all described stages.ConclusionsWe announce a detailed data on the earliest events in D. gyrociliatus and D. taeniatus neurodevelopment based on anti-acetylated tubulin, serotonin, and FMRFamide-like immuno labeling. The first nerve elements demonstrate no 5-HT-IR and no FMRFa-IR, which differs from the most Polychaetes and even Lophotrochozoans, investigated so far. Moreover, these animals do not have a typical apical organ (or perhaps do not have it at all) and the pioneer neurons of D.gyrociliatus are also peculiar in that they join the definitive nervous system unlike other lophotrochozoans where pioneer nerons are transient. Thus, Dinophilus neurogenesis demonstrates a variation of common scheme. The reported study was funded by RFBR, project number 19-3460040.

Download Full-text

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans

10.1101/148080 ◽

2017 ◽

Author(s):

Byunghyuk Kim ◽

Scott W. Emmons

Keyword(s):

Nervous System ◽

Cell Adhesion ◽

Sensory Neuron ◽

Protein Interactions ◽

Synapse Formation ◽

System Development ◽

Nervous System Development ◽

Surface Proteins ◽

C Elegans ◽

Nervous System Function

ABSTRACTNervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

Download Full-text

Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit in C. elegans

eLife ◽

10.7554/elife.29257 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 19

Author(s):

Byunghyuk Kim ◽

Scott W Emmons

Keyword(s):

Nervous System ◽

Cell Adhesion ◽

Sensory Neuron ◽

Protein Interactions ◽

Synapse Formation ◽

System Development ◽

Nervous System Development ◽

Surface Proteins ◽

C Elegans ◽

Nervous System Function

Nervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity in C. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.

Download Full-text

The Role of Chondroitin Sulfate Proteoglycans in Nervous System Development

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420959147 ◽

2020 ◽

Vol 69 (1) ◽

pp. 61-80 ◽

Cited By ~ 1

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:

Download Full-text

Role of miRNA-mRNA Interaction in Neural Stem Cell Differentiation of Induced Pluripotent Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21196980 ◽

2020 ◽

Vol 21 (19) ◽

pp. 6980

Author(s):

Satish Kumar ◽

Joanne E. Curran ◽

Erica DeLeon ◽

Ana C. Leandro ◽

Tom E. Howard ◽

...

Keyword(s):

Nervous System ◽

Synapse Formation ◽

System Development ◽

Target Prediction ◽

Stem Cell Differentiation ◽

Nervous System Development ◽

P Value ◽

Protein Coding ◽

Human Ipscs

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10−15–1.44 × 10−4). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease.

Download Full-text

The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning

PLoS Genetics ◽

10.1371/journal.pgen.1009475 ◽

2021 ◽

Vol 17 (7) ◽

pp. e1009475

Author(s):

Leo T. H. Tang ◽

Meera Trivedi ◽

Jenna Freund ◽

Christopher J. Salazar ◽

Maisha Rahman ◽

...

Keyword(s):

Nervous System ◽

Neuronal Development ◽

System Development ◽

Nervous System Development ◽

Axonal Guidance ◽

Neural Patterning ◽

Dendritic Trees ◽

Important Regulator ◽

P Type ◽

Dendrite Morphogenesis

The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the catp-8/P5A-ATPase as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the Caenorhabditis elegans ortholog catp-8/P5A-ATPase is required for defined aspects of nervous system development. Specifically, the catp-8/P5A-ATPase serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, catp-8/P5A-ATPase is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require catp-8/P5A-ATPase, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require catp-8/P5A-ATPase. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and catp-8/P5A-ATPase can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that catp-8/P5A-ATPase can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that catp-8/P5A-ATPase is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that catp-8/P5A-ATPase serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments.

Download Full-text