Integrin alpha 6 expression is required for early nervous system development in Xenopus laevis

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2539-2554 ◽  
Author(s):  
T.E. Lallier ◽  
C.A. Whittaker ◽  
D.W. DeSimone
Keyword(s):  
Nervous System ◽  
Early Development ◽  
System Development ◽  
Cranial Nerves ◽  
Nervous System Development ◽  
Neural Plate ◽  
Pronephric Duct ◽  
Axial Defects ◽  
Integrin Alpha 6

The integrin alpha 6 subunit pairs with both the beta 1 and beta 4 subunits to form a subfamily of laminin receptors. Here we report the cDNA cloning and primary sequence for the Xenopus homologue of the mammalian integrin alpha 6 subunit. We present data demonstrating the spatial and temporal expression of alpha 6 mRNA and protein during early development. Initially, alpha 6 transcripts are expressed in the dorsal ectoderm and future neural plate at the end of gastrulation. Later in development, alpha 6 mRNAs are expressed in a variety of neural derivatives, including the developing sensory placodes (otic and olfactory) and commissural neurons within the neural tube. Integrin alpha 6 is also expressed in the elongating pronephric duct as well as a subset of the rhombencephalic neural crest, which will form the Schwann cells lining several cranial nerves (VII, VIII and X). In vivo expression of an alpha 6 antisense transcript in the animal hemisphere leads to a reduction in alpha 6 protein expression, a loss of adhesion to laminin, and severe defects in normal development. In 35% of cases, reduced levels of alpha 6 expression result in embryos that complete gastrulation normally but arrest at neurulation prior to the formation of the neural plate. In an additional 22% of cases, embryos develop with severe axial defects, including complete loss of head or tail structures. In contrast, overexpression of the alpha 6 subunit by injection of full-length mRNA has no apparent effect on embryonic development. Co-injection of antisense and sense plasmid constructs results in a partial rescue of the antisense-generated phenotypes. These data indicate that the integrin alpha 6 subunit is critical for the early development of the nervous system in amphibians.

scholarly journals Drosophila Stathmin: A Microtubule-destabilizing Factor Involved in Nervous System Formation

2002 ◽  
Vol 13 (2) ◽  
pp. 698-710 ◽  
Author(s):  
Sylvie Ozon ◽  
Antoine Guichet ◽  
Olivier Gavet ◽  
Siegfried Roth ◽  
André Sobel
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
Microtubule Assembly ◽  
Nervous Systems ◽  
Germ Cell Migration ◽  
Numerous Cell ◽  
First Time

Stathmin is a ubiquitous regulatory phosphoprotein, the generic element of a family of neural phosphoproteins in vertebrates that possess the capacity to bind tubulin and interfere with microtubule dynamics. Although stathmin and the other proteins of the family have been associated with numerous cell regulations, their biological roles remain elusive, as in particular inactivation of the stathmin gene in the mouse resulted in no clear deleterious phenotype. We identified stathmin phosphoproteins inDrosophila, encoded by a unique gene sharing the intron/exon structure of the vertebrate stathmin andstathmin family genes. They interfere with microtubule assembly in vitro, and in vivo when expressed in HeLa cells. Drosophila stathmin expression is regulated during embryogenesis: it is high in the migrating germ cells and in the central and peripheral nervous systems, a pattern resembling that of mammalian stathmin. Furthermore, RNA interference inactivation ofDrosophila stathmin expression resulted in germ cell migration arrest at stage 14. It also induced important anomalies in nervous system development, such as loss of commissures and longitudinal connectives in the ventral cord, or abnormal chordotonal neuron organization. In conclusion, a single Drosophilagene encodes phosphoproteins homologous to the entire vertebrate stathmin family. We demonstrate for the first time their direct involvement in major biological processes such as development of the reproductive and nervous systems.

scholarly journals Vitamin E is Necessary to Protect Neural Crest Cells in Developing Zebrafish Embryos

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1209-1209
Author(s):  
Brian Head ◽  
Jane La Du ◽  
Robyn Tanguay ◽  
Chrissa Kioussi ◽  
Maret Traber
Keyword(s):  
Nervous System ◽  
Vitamin E ◽  
Neural Crest ◽  
System Development ◽  
Neural Crest Cells ◽  
Nervous System Development ◽  
Neural Plate ◽  
Zebrafish Embryos ◽  
Normal Brain ◽  
Collagen Formation

Abstract Objectives Vitamin E (VitE) deficiency causes vertebrate embryonic lethality. The alpha-tocopherol transfer protein (Ttpa) likely regulates VitE distribution in the early zebrafish embryo because Ttpa knockdown causes impaired nervous system development and embryonic death by 15–18 hours post-fertilization (hpf). We propose that VitE is necessary for normal brain and peripheral nervous system development. Methods Zebrafish embryos are obtained from adults fed either VitE sufficient (E+) or deficient (E–) diets for at least 80 days. Embryos at 12 and 24 hpf are subjected to RNA whole mount in situ hybridization (WISH). RNA is also collected from embryos at 12, 18 and 24 hpf for RT-qPCR of specific targets. Results At 12 hpf, the midbrain-hindbrain boundary and otic placodes are malformed in E– embryos, as shown by Pax2a expression. Similarly, Sox10 expression shows that E– embryos lack clear neural plate borders. Nonetheless, in 12 hpf E + and E− embryos Ttpa is localized similarly throughout the nervous system. Pax2a expression initiates collagen formation in the developing notochord. Collagen genes, col2a1a and col9a2, expression patterns showed abnormal notochord structures in 24 hpf E– embryos. At 24 hpf in E + embryos, Sox10 expressing-neural crest cells are localized both in the central nervous system and dorsal root ganglia (DRG), while the Sox10 signal is diminished in E– embryos in both the DRG and early enteric nervous system. At 24 hpf, Ttpa expression outlines the brain ventricle borders; critically E– embryos show reduced Ttpa signal and impaired ventricle closing. Gene expression by qPCR will be used to confirm these results. Conclusions This VitE deficient embryo model suggests that the carefully programmed development of the nervous system is distorted due to lack of adequate VitE. Thus, Ttpa and VitE are critical molecules for neural plate and neural tube formation, and neural crest cell migration. Funding Sources The authors received no specific funding for this work.

scholarly journals Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo

2006 ◽  
Vol 11 (5) ◽  
pp. 054022 ◽  
Author(s):  
Szu-Yu Chen ◽  
Cho-Shuen Hsieh ◽  
Shi-Wei Chu ◽  
Cheng-Yung Lin ◽  
Ching-Yi Ko ◽  
...  
Keyword(s):  
Nervous System ◽  
Optical Microscopy ◽  
System Development ◽  
Nervous System Development ◽  
Embryonic Nervous System ◽  
Long Term Observation

scholarly journals Delayed Development of Nervous System in Mice Homozygous for Disrupted Microtubule-associated Protein 1B (MAP1B) Gene

1997 ◽  
Vol 137 (7) ◽  
pp. 1615-1626 ◽  
Author(s):  
Yosuke Takei ◽  
Satoru Kondo ◽  
Akihiro Harada ◽  
Satomi Inomata ◽  
Tetsuo Noda ◽  
...  
Keyword(s):  
Nervous System ◽  
Gene Targeting ◽  
Time Course ◽  
System Development ◽  
Nervous System Development ◽  
Dominant Negative ◽  
Gene Encoding ◽  
Neuronal Morphogenesis ◽  
Associated Proteins

Microtubule-associated protein 1B (MAP1B), one of the microtubule-associated proteins (MAPs), is a major component of the neuronal cytoskeleton. It is expressed at high levels in immature neurons during growth of their axons, which indicates that it plays a crucial role in neuronal morphogenesis and neurite extension. To better define the role of MAP1B in vivo, we have used gene targeting to disrupt the murine MAP1B gene. Heterozygotes of our MAP1B disruption exhibit no overt abnormalities in their development and behavior, while homozygotes showed a slightly decreased brain weight and delayed nervous system development. Our data indicate that while MAP1B is not essential for survival, it is essential for normal time course development of the murine nervous system. These conclusions are very different from those of a previous MAP1B gene–targeting study (Edelmann, W., M. Zervas, P. Costello, L. Roback, I. Fischer, A. Hammarback, N. Cowan, P. Davis, B. Wainer, and R. Kucherlapati. 1996. Proc. Natl. Acad. Sci. USA. 93: 1270–1275). In this previous effort, homozygotes died before reaching 8-d embryos, while heterozygotes showed severely abnormal phenotypes in their nervous systems. Because the gene targeting event in these mice produced a gene encoding a 571–amino acid truncated product of MAP1B, it seems likely that the phenotypes seen arise from the truncated MAP1B product acting in a dominant-negative fashion, rather than a loss of MAP1B function.

scholarly journals Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009698
Author(s):  
Laura E. Kuil ◽  
Katherine C. MacKenzie ◽  
Clara S. Tang ◽  
Jonathan D. Windster ◽  
Thuy Linh Le ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Copy Number ◽  
System Development ◽  
Hirschsprung Disease ◽  
Nervous System Development ◽  
Gene Enrichment ◽  
Coding Variants ◽  
Enteric Nervous System Development

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses—often de novo—contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease.

scholarly journals TDP-43 in central nervous system development and function: clues to TDP-43-associated neurodegeneration

2012 ◽  
Vol 393 (7) ◽  
pp. 589-594 ◽  
Author(s):  
Chantelle F. Sephton ◽  
Basar Cenik ◽  
Bercin Kutluk Cenik ◽  
Joachim Herz ◽  
Gang Yu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Interactions ◽  
System Development ◽  
Nervous System Development ◽  
Rna Targets ◽  
The Central Nervous System ◽  
And Function ◽  
Lateral Sclerosis

Abstract From the earliest stages of embryogenesis and throughout life, transcriptional regulation is carefully orchestrated in order to generate, shape, and reshape the central nervous system (CNS). TAR DNA-binding protein 43 (TDP-43) is identified as a regulator of essential transcriptional events in the CNS. Evidence for its importance comes from the identification of TDP-43 protein aggregates and genetic mutations in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Efforts are being made to learn more about the biological function of TDP-43 and gain a better understanding of its role in neurodegeneration. TDP-43 RNA targets and protein interactions have now been identified, and in vivo evidence shows that TDP-43 is essential in CNS development and function. This review will highlight aspects of these findings.

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 Role of kinesin-1–based microtubule sliding in Drosophila nervous system development

2016 ◽  
Vol 113 (34) ◽  
pp. E4985-E4994 ◽  
Author(s):  
Michael Winding ◽  
Michael T. Kelliher ◽  
Wen Lu ◽  
Jill Wildonger ◽  
Vladimir I. Gelfand
Keyword(s):  
Nervous System ◽  
Binding Site ◽  
Heavy Chain ◽  
System Development ◽  
Nervous System Development ◽  
Axon Outgrowth ◽  
Organelle Transport ◽  
Genomic Locus

The plus-end microtubule (MT) motor kinesin-1 is essential for normal development, with key roles in the nervous system. Kinesin-1 drives axonal transport of membrane cargoes to fulfill the metabolic needs of neurons and maintain synapses. We have previously demonstrated that kinesin-1, in addition to its well-established role in organelle transport, can drive MT–MT sliding by transporting “cargo” MTs along “track” MTs, resulting in dramatic cell shape changes. The mechanism and physiological relevance of this MT sliding are unclear. In addition to its motor domain, kinesin-1 contains a second MT-binding site, located at the C terminus of the heavy chain. Here, we mutated this C-terminal MT-binding site such that the ability of kinesin-1 to slide MTs is significantly compromised, whereas cargo transport is unaffected. We introduced this mutation into the genomic locus of kinesin-1 heavy chain (KHC), generating the KhcmutA allele. KhcmutA neurons displayed significant MT sliding defects while maintaining normal transport of many cargoes. Using this mutant, we demonstrated that MT sliding is required for axon and dendrite outgrowth in vivo. Consistent with these results, KhcmutA flies displayed severe locomotion and viability defects. To test the role of MT sliding further, we engineered a chimeric motor that actively slides MTs but cannot transport organelles. Activation of MT sliding in KhcmutA neurons using this chimeric motor rescued axon outgrowth in cultured neurons and in vivo, firmly establishing the role of sliding in axon outgrowth. These results demonstrate that MT sliding by kinesin-1 is an essential biological phenomenon required for neuronal morphogenesis and normal nervous system development.

scholarly journals CD60b: Enriching Neural Stem/Progenitor Cells from Rat Development into Adulthood

2017 ◽  
Vol 2017 ◽  
pp. 1-16
Author(s):  
Fernanda Gubert ◽  
Camila Zaverucha-do-Valle ◽  
Michelle Furtado ◽  
Pedro M. Pimentel-Coelho ◽  
Nicoli Mortari ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Neurogenic Niche ◽  
Neural Stem Progenitor Cells

CD60b antigens are highly expressed during development in the rat nervous system, while in the adult their expression is restricted to a few regions, including the subventricular zone (SVZ) around the lateral ventricles—a neurogenic niche in the adult brain. For this reason, we investigated whether the expression of C60b is associated with neural stem/progenitor cells in the SVZ, from development into adulthood. We performedin vitroandin vivoanalyses of CD60b expression at different stages and identified the presence of these antigens in neural stem/progenitor cells. We also observed that CD60b could be used to purify and enrich a population of neurosphere-forming cells from the developing and adult brain. We showed that CD60b antigens (mainly corresponding to ganglioside 9-O-acetyl GD3, a well-known molecule expressed during central nervous system development and mainly associated with neuronal migration) are also present in less mature cells and could be used to identify and isolate neural stem/progenitor cells during development and in the adult brain. A better understanding of molecules associated with neurogenesis may contribute not only to improve the knowledge about the physiology of the mammalian central nervous system, but also to find new treatments for regenerating tissue after disease or brain injury.

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