scholarly journals Cell-specific expression and individual function of prohormone convertase PC1/3 in Tribolium larval growth highlights major evolutionary changes between beetle and fly neuroendocrine systems

EvoDevo ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sonja Fritzsche ◽  
Vera S. Hunnekuhl
Keyword(s):  
Larval Growth ◽  
Neuroendocrine System ◽  
Small Subset ◽  
Specific Cell ◽  
Specific Expression ◽  
Individual Function ◽  
Evolutionary Changes ◽  
Cell Groups ◽  
Cell Type Specific Expression ◽  
And Function

Abstract Background The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates, ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome. Results In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient yolk to the developing oocytes. Larval RNAi against PC2 produced moulting defects where the larvae were not able to shed their old cuticle. This ecdysis phenotype was also observed in a small subset of PC1/3 knockdown larvae and was strongest in a double knockdown. Unexpectedly, most PC1/3-RNAi larvae showed strongly reduced growth, but went through larval moults despite minimal to zero weight gain. Conclusions The cell type-specific expression of PC1/3 and its essential requirement for larval growth highlight the important role of this gene within the insect neuroendocrine system. Genomic conservation in most insect groups suggests that it has a comparable individual function in other insects as well, which has been replaced by alternative mechanisms in flies.

scholarly journals Individual function of the ancestral prohormone convertase PC1/3 in Tribolium larval growth and moulting highlights major evolutionary changes between beetle and fly neuroendocrine systems

2020 ◽  
Author(s):  
Sonja Fritzsche ◽  
Vera Sophie Hunnekuhl
Keyword(s):  
Gene Loss ◽  
Larval Growth ◽  
Specific Cell ◽  
Insect Larvae ◽  
Individual Function ◽  
Evolutionary Changes ◽  
Cell Groups ◽  
And Function ◽  
Redundant Functions ◽  
Biological Differences

Abstract Background: The insect neuroendocrine system acts in the regulation of physiology, development and growth. Molecular evolution of this system hence has the potential to allow for major biological differences between insect groups. Two prohormone convertases, PC1/3 and PC2, are found in animals and both function in the processing of neuropeptide precursors in the vertebrate neurosecretory pathway. Whereas PC2-function is conserved between the fly Drosophila and vertebrates , ancestral PC1/3 was lost in the fly lineage and has not been functionally studied in any protostome. Results: In order to understand its original functions and the changes accompanying the gene loss in the fly, we investigated PC1/3 and PC2 expression and function in the beetle Tribolium castaneum. We found that PC2 is broadly expressed in the nervous system, whereas surprisingly, PC1/3 expression is restricted to specific cell groups in the posterior brain and suboesophageal ganglion. Both proteases have parallel but non-redundant functions in adult beetles’ viability and fertility. Female infertility following RNAi is caused by a failure to deposit sufficient nutritive material to the developing oocytes. Larval RNAi of both genes produced moulting defects where the larvae were not able to shed their old cuticle and became ‘locked-in’. Unexpectedly, PC1/3 RNAi larvae went through supernumerary larval moults despite minimal to zero weight gain. Conclusions: Our results indicate a yet unknown molecular mechanism for the coupling of moulting and growth in insect larvae. Conservation of the evolutionary ancient PC1/3 gene in most insect groups suggests conserved function and that its loss in dipterans may have been accompanied by major changes in the coordination of larval growth and moulting.

scholarly journals Adeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation

2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Cell Types ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Specific Expression ◽  
Adeno Associated Virus ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Novel Applications

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.

scholarly journals Function of Circular RNAs in Fish and Their Potential Application as Biomarkers

2021 ◽  
Vol 22 (13) ◽  
pp. 7119
Author(s):  
Golam Rbbani ◽  
Artem Nedoluzhko ◽  
Jorge Galindo-Villegas ◽  
Jorge M. O. Fernandes
Keyword(s):  
Growth Regulation ◽  
Functional Characterization ◽  
Circular Rnas ◽  
Farmed Fish ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Taxonomic Groups ◽  
And Function

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

Viral Strategies for Targeting the Central and Peripheral Nervous Systems

2018 ◽  
Vol 41 (1) ◽  
pp. 323-348 ◽  
Author(s):  
Claire N. Bedbrook ◽  
Benjamin E. Deverman ◽  
Viviana Gradinaru
Keyword(s):  
Nervous System ◽  
Regulatory Elements ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Recombinant Viruses ◽  
Neuronal Populations ◽  
Neuroscience Research ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type–specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.

scholarly journals Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis

2019 ◽  
Vol 21 (1) ◽  
pp. 132 ◽  
Author(s):  
Hironori Matsuyama ◽  
Hiroshi I. Suzuki
Keyword(s):  
Expression Patterns ◽  
System Level ◽  
Mirna Biogenesis ◽  
Mirna Regulation ◽  
Specific Expression ◽  
Synthetic Gene Circuits ◽  
Mirna Genes ◽  
Super Enhancer ◽  
Cell Type Specific Expression ◽  
And Function

MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA–target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.

Cerebellar histogenesis is disturbed in mice lacking cyclin D2

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1927-1935 ◽  
Author(s):  
J.M. Huard ◽  
C.C. Forster ◽  
M.L. Carter ◽  
P. Sicinski ◽  
M.E. Ross
Keyword(s):  
Granule Cell ◽  
Molecular Layer ◽  
Stellate Cells ◽  
Cell Types ◽  
Cell Number ◽  
Specific Cell ◽  
Cyclin D2 ◽  
Specific Expression ◽  
Precursor Pool ◽  
Cell Type Specific Expression

Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonstrated for cyclin D2, may contribute to these processes. If so, regional brain development should be affected by alteration of cyclin expression. To test this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin primarily affected two neuronal populations: granule cell number was reduced and stellate interneurons were nearly absent. Differences between null and wild-type siblings were obvious by the second postnatal week. Decreases in granule cell number arose from both reduction in primary neurogenesis and increase in apoptosis of cells that fail to differentiate. The dearth of stellate cells in the molecular layer indicates that emergence of this subpopulation requires cyclin D2 expression. Surprisingly, Golgi and basket interneurons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cerebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons.

scholarly journals Transsynaptic Fish-lips signaling prevents misconnections between nonsynaptic partner olfactory neurons

2019 ◽  
Vol 116 (32) ◽  
pp. 16068-16073 ◽  
Author(s):  
Qijing Xie ◽  
Bing Wu ◽  
Jiefu Li ◽  
Chuanyun Xu ◽  
Hongjie Li ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Transmembrane Protein ◽  
Small Subset ◽  
Projection Neurons ◽  
Specific Expression ◽  
Olfactory Neurons ◽  
Surface Molecules ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Receptor Neurons

Our understanding of the mechanisms of neural circuit assembly is far from complete. Identification of wiring molecules with novel mechanisms of action will provide insights into how complex and heterogeneous neural circuits assemble during development. In the Drosophila olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of partner projection neurons (PNs). Here, we performed an RNA interference screen for cell surface molecules and identified the leucine-rich repeat–containing transmembrane protein known as Fish-lips (Fili) as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise axon and dendrite targeting of a small subset of ORN and PN classes, respectively. Cell-type–specific expression and genetic analyses suggest that Fili sends a transsynaptic repulsive signal to neurites of nonpartner classes that prevents their targeting to inappropriate glomeruli in the antennal lobe.

scholarly journals Cell Type-specific Expression of the Mas Proto-oncogene in Testis

2002 ◽  
Vol 50 (5) ◽  
pp. 691-695 ◽  
Author(s):  
Natalia Alenina ◽  
Tatjana Baranova ◽  
Eugene Smirnow ◽  
Michael Bader ◽  
Andrea Lippoldt ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Rnase Protection Assay ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Specific Expression ◽  
Rnase Protection ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
And Function ◽  
Old Mice

The Mas proto-oncogene encodes a G-protein-coupled receptor with the common seven transmembrane domains and may be involved in the actions of angiotensins. Because Mas is highly expressed in testis, we investigated the cell type-specificity and the onset of expression of the gene in this organ. Using an RNase protection assay, it could be shown that neither whole testes nor cultured Sertoli and Leydig cells of 12-day-old mice express Mas mRNA. Mas expression is first detected in 18-day-old mice and thereafter increases continuously until 6 months of age. By in situ hybridization, the expression could be localized to Leydig cells and Sertoli cells, the signals being much more pronounced in the former. A weak signal was detected in primary spermatocytes. The strong ontogenetically controlled and cell type-specific expression of this membrane-bound receptor in testis implicates a role for the Mas proto-oncogene in testis maturation and function.

scholarly journals Genomics at cellular resolution: insights into cognitive disorders and their evolution

2020 ◽  
Vol 29 (R1) ◽  
pp. R1-R9
Author(s):  
Stefano Berto ◽  
Yuxiang Liu ◽  
Genevieve Konopka
Keyword(s):  
Cognitive Disorders ◽  
Brain Evolution ◽  
Cell Types ◽  
Autism Spectrum ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Variant Information ◽  
Cell Type Specific ◽  
And Function

Abstract High-throughput genomic sequencing approaches have held the promise of understanding and ultimately leading to treatments for cognitive disorders such as autism spectrum disorders, schizophrenia and Alzheimer’s disease. Although significant progress has been made into identifying genetic variants associated with these diseases, these studies have also uncovered that these disorders are mostly genetically complex and thus challenging to model in non-human systems. Improvements in such models might benefit from understanding the evolution of the human genome and how such modifications have affected brain development and function. The intersection of genome-wide variant information with cell-type-specific expression and epigenetic information will further assist in resolving the contribution of particular cell types in evolution or disease. For example, the role of non-neuronal cells in brain evolution and cognitive disorders has gone mostly underappreciated until the recent availability of single-cell transcriptomic approaches. In this review, we discuss recent studies that carry out cell-type-specific assessments of gene expression in brain tissue across primates and between healthy and disease populations. The emerging results from these studies are beginning to elucidate how specific cell types in the evolved human brain are contributing to cognitive disorders.

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