Formation of neuroblasts in the embryonic central nervous system of Drosophila melanogaster is controlled by SoxNeuro

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4193-4203 ◽  
Author(s):  
Marita Buescher ◽  
Fook Sion Hing ◽  
William Chia
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Neural Progenitor Cells ◽  
Loss Of Function ◽  
Dorsoventral Patterning ◽  
Sox Proteins ◽  
The Central Nervous System ◽  
Modulation Of Gene Expression ◽  
Determining Factor

Sox proteins form a family of HMG-box transcription factors related to the mammalian testis determining factor SRY. Sox-mediated modulation of gene expression plays an important role in various developmental contexts. Drosophila SoxNeuro, a putative ortholog of the vertebrate Sox1, Sox2 and Sox3 proteins, is one of the earliest transcription factors to be expressed pan-neuroectodermally. We demonstrate that SoxNeuro is essential for the formation of the neural progenitor cells in central nervous system. We show that loss of function mutations of SoxNeuro are associated with a spatially restricted hypoplasia: neuroblast formation is severely affected in the lateral and intermediate regions of the central nervous system, whereas ventral neuroblast formation is almost normal. We present evidence that a requirement for SoxNeuro in ventral neuroblast formation is masked by a functional redundancy with Dichaete, a second Sox protein whose expression partially overlaps that of SoxNeuro. Genetic interactions of SoxNeuro and the dorsoventral patterning genes ventral nerve chord defective and intermediate neuroblasts defective underlie ventral and intermediate neuroblast formation. Finally, the expression of the Achaete-Scute gene complex suggests that SoxNeuro acts upstream and in parallel with the proneural genes.

scholarly journals Crazy Little Thing Called Sox—New Insights in Oligodendroglial Sox Protein Function

2019 ◽  
Vol 20 (11) ◽  
pp. 2713 ◽  
Author(s):  
Jan Wittstatt ◽  
Simone Reiprich ◽  
Melanie Küspert
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Protein Function ◽  
Target Genes ◽  
Demyelinating Diseases ◽  
Chromatin Remodelers ◽  
Sox Proteins ◽  
The Central Nervous System ◽  
And Migration

In the central nervous system, oligodendrocytes wrap axons with myelin sheaths, which is essential for rapid transfer of electric signals and their trophic support. In oligodendroglia, transcription factors of the Sox protein family are pivotal regulators of a variety of developmental processes. These include specification, proliferation, and migration of oligodendrocyte precursor cells as well as terminal differentiation to mature myelinating oligodendrocytes. Sox proteins are further affected in demyelinating diseases and are involved in remyelination following damage of the central nervous system. Here we summarize and discuss latest findings on transcriptional regulation of Sox proteins, their function, target genes, and interaction with other transcription factors and chromatin remodelers in oligodendroglia with physiological and pathophysiological relevance.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

Design, fabrication, and testing of a bioprinted nerve graft

2016 ◽  
Author(s):  
◽  
Christopher M. Owens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Graft ◽  
Loss Of Function ◽  
Vitro Assay ◽  
Central Nervous System Damage ◽  
In Vivo Animal Model ◽  
The Central Nervous System

Injuries to nerves vary in their consequences, from weakened sensation and motor function to partial or complete paralysis. In the latter case, affecting about twenty thousand Americans yearly, the injury is debilitating and results in a significant decrease in quality of life. Currently there is no effective treatment for damage to the central nervous system, in particular the spinal cord. Compared to the injuries to the central nervous system, damage in the peripheral nerves, is more common, with about sixty thousand occurrences annually. The cost of associated surgical procedures and due to loss of function is in the billions. In this thesis we present work towards the construction and testing of a fully cellular, patented nerve graft, one amongst the first of its kind. For the fabrication of the graft we are the first to employ bioprinting (either implemented through a special purpose 3D bioprinter or manually), a novel tissue engineering method rapidly gaining acceptance and utility. We first review the status of bioprinting. We then detail the fabrication process. Next we report on the testing of the graft in an in vivo animal model through electrophysiology and histology. This is followed by the introduction of a novel in vitro model, aimed at providing a fast, inexpensive and reliable method to test engineered nerve grafts. We describe our work on the optimization of the in vitro assay and then the testing of the graft using the optimized assay. We conclude with a summary of our accomplishments and make suggestions for some exciting future applications of our approach.

scholarly journals A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system

2019 ◽  
Vol 37 (8) ◽  
pp. 884-894 ◽  
Author(s):  
Julia F. Alterman ◽  
Bruno M. D. C. Godinho ◽  
Matthew R. Hassler ◽  
Chantal M. Ferguson ◽  
Dimas Echeverria ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
The Central Nervous System ◽  
Modulation Of Gene Expression

scholarly journals A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion

2001 ◽  
Vol 155 (7) ◽  
pp. 1117-1122 ◽  
Author(s):  
Greg J. Bashaw ◽  
Hailan Hu ◽  
Catherine D. Nobes ◽  
Corey S. Goodman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Rho Gtpases ◽  
Ectopic Expression ◽  
Nucleotide Exchange ◽  
Loss Of Function ◽  
Guanine Nucleotide Exchange ◽  
Positive Regulators ◽  
The Central Nervous System ◽  
Rho Gef

The key role of the Rho family GTPases Rac, Rho, and CDC42 in regulating the actin cytoskeleton is well established (Hall, A. 1998. Science. 279:509–514). Increasing evidence suggests that the Rho GTPases and their upstream positive regulators, guanine nucleotide exchange factors (GEFs), also play important roles in the control of growth cone guidance in the developing nervous system (Luo, L. 2000. Nat. Rev. Neurosci. 1:173–180; Dickson, B.J. 2001. Curr. Opin. Neurobiol. 11:103–110). Here, we present the identification and molecular characterization of a novel Dbl family Rho GEF, GEF64C, that promotes axon attraction to the central nervous system midline in the embryonic Drosophila nervous system. In sensitized genetic backgrounds, loss of GEF64C function causes a phenotype where too few axons cross the midline. In contrast, ectopic expression of GEF64C throughout the nervous system results in a phenotype in which far too many axons cross the midline, a phenotype reminiscent of loss of function mutations in the Roundabout (Robo) repulsive guidance receptor. Genetic analysis indicates that GEF64C expression can in fact overcome Robo repulsion. Surprisingly, evidence from genetic, biochemical, and cell culture experiments suggests that the promotion of axon attraction by GEF64C is dependent on the activation of Rho, but not Rac or Cdc42.

scholarly journals RFX4 transcription factor regulates IFT172 expression, cilia formation and dorsoventral patterning of the central nervous system

2007 ◽  
Vol 306 (1) ◽  
pp. 360
Author(s):  
Amir M. Ashique ◽  
Mattias Karlen ◽  
Youngshik Choe ◽  
Johan Ericson ◽  
John L. Rubenstein ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Dorsoventral Patterning ◽  
Cilia Formation ◽  
The Central Nervous System

The Loss of Function Following on Lesions of the Central Nervous System [Ueber Die Ausfallerscheinungen nach Läsionen Des Central Nervensystems]. (Neurol. Cbl., Nr. 13, 1907.) Rothmann, Max

1908 ◽  
Vol 54 (225) ◽  
pp. 146-148
Author(s):  
William W. Ireland
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Lower Portion ◽  
Loss Of Function ◽  
Cerebral Ganglia ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Central Lesions

Rothmann points out how important it is to surgeons that the localisation of lesions in the brain and spinal cord should be made with the utmost accuracy. In many cases diseases do not strike suddenly upon a nervous system previously intact. Often the circulation has been previously deranged by arterial sclerosis, which prepares the way for transitory hemiplegia or aphasia. Sometimes there is loss of function after central lesions, which disappears in longer or shorter time. Goltz and his followers have treated many effects following the extirpation of the whole or part of the cerebrum as due to what they call inhibition (Hemmung). Thus the functions of the spinal cord are much impaired after removal of the cerebral ganglia, or the lower portion of the cord loses its reflex function after section higher up, but after a while it again resumes its act$ibon.

The Drosophila Ras2 and Rop gene pair: a dual homology with a yeast Ras-like gene and a suppressor of its loss-of-function phenotype

Development ◽  
1993 ◽  
Vol 117 (4) ◽  
pp. 1309-1319 ◽  
Author(s):  
A. Salzberg ◽  
N. Cohen ◽  
N. Halachmi ◽  
Z. Kimchie ◽  
Z. Lev
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Vesicle Trafficking ◽  
Bidirectional Promoter ◽  
Opposite Polarity ◽  
Loss Of Function ◽  
Cis Acting ◽  
The Central Nervous System ◽  
Cellular Compartments ◽  
Drosophila Cells

The promoter of the Drosophila melanogaster Ras2 gene is bidirectional, regulating an additional gene oriented in the opposite polarity. The two divergently transcribed genes are only 93 bases apart and deletion analysis proved that common cis-acting elements within this promoter region are required for the transcriptional activity of both genes. We cloned the gene paired with Ras2 in the bidirectional promoter and isolated cDNAs corresponding to its mRNA. The Ras opposite (Rop) gene encodes for a 68 × 10(3) M(r) protein which shares sequence homology with the members of a novel Saccharomyces cerevisiae gene family, including the SLY1, SEC1 and VPS33 (SLP1) genes, all of which are involved in vesicle trafficking among yeast cellular compartments. A highly conserved motif in this family is also found in beta-COP, a coat protein isolated from rat Golgi-bound nonclathrin vesicles. Thus, the Rop protein may be a component of one of the vesicle trafficking pathways in Drosophila cells. The Rop gene expression during embryogenesis is restricted to the central nervous system (CNS) and the garland cells, a small group of nephrocytes that takes up waste materials from the haemolymph by endocytosis. Ras2 is also expressed in the embryonic garland cells. In postembryonic stages, the two genes are co-expressed in the larval salivary glands and the central nervous system, and in the adult CNS and reproductive systems. Interestingly, the S. cerevisiae SLY1-20 allele is a suppressor of the loss of the YPT1 gene, a ras-like gene implicated in vesicle translocation, suggesting that the two genes may interact with one another. Since Sec1p and beta-COP may also interact with small GTP-binding proteins of the ras superfamily, it is conceivable that the Rop and Ras2 gene products are not just co-expressed in common tissues, but may also functionally interact with one another in these tissues.

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