scholarly journals Retinal axon guidance by region-specific cues in diencephalon

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 791-801 ◽  
Author(s):  
R. Tuttle ◽  
J.E. Braisted ◽  
L.J. Richards ◽  
D.D. O'Leary
Keyword(s):  
Extracellular Matrix ◽  
Axon Guidance ◽  
Axon Growth ◽  
Floor Plate ◽  
Retinal Axons ◽  
Stimulatory Activity ◽  
Extracellular Matrix Molecules ◽  
Retinal Axon

Retinal axons show region-specific patterning along the dorsal-ventral axis of diencephalon: retinal axons grow in a compact bundle over hypothalamus, dramatically splay out over thalamus, and circumvent epithalamus as they continue toward the dorsal midbrain. In vitro, retinal axons are repulsed by substrate-bound and soluble activities in hypothalamus and epithalamus, but invade thalamus. The repulsion is mimicked by a soluble floor plate activity. Tenascin and neurocan, extracellular matrix molecules that inhibit retinal axon growth in vitro, are enriched in hypothalamus and epithalamus. Within thalamus, a stimulatory activity is specifically upregulated in target nuclei at the time that retinal axons invade them. These findings suggest that region-specific, axon repulsive and stimulatory activities control retinal axon patterning in the embryonic diencephalon.

Retinal axon growth cones respond to EphB extracellular domains as inhibitory axon guidance cues

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 3041-3048 ◽  
Author(s):  
Eric Birgbauer ◽  
Stephen F. Oster ◽  
Christophe G. Severin ◽  
David W. Sretavan
Keyword(s):  
Axon Guidance ◽  
Optic Disc ◽  
Growth Cone ◽  
Axon Growth ◽  
Growth Cones ◽  
Axon Pathfinding ◽  
Guidance Cues ◽  
Extracellular Domains ◽  
Retinal Axons ◽  
Retinal Axon

Axon pathfinding relies on cellular signaling mediated by growth cone receptor proteins responding to ligands, or guidance cues, in the environment. Eph proteins are a family of receptor tyrosine kinases that govern axon pathway development, including retinal axon projections to CNS targets. Recent examination of EphB mutant mice, however, has shown that axon pathfinding within the retina to the optic disc is dependent on EphB receptors, but independent of their kinase activity. Here we show a function for EphB1, B2 and B3 receptor extracellular domains (ECDs) in inhibiting mouse retinal axons when presented either as substratum-bound proteins or as soluble proteins directly applied to growth cones via micropipettes. In substratum choice assays, retinal axons tended to avoid EphB-ECDs, while time-lapse microscopy showed that exposure to soluble EphB-ECD led to growth cone collapse or other inhibitory responses. These results demonstrate that, in addition to the conventional role of Eph proteins signaling as receptors, EphB receptor ECDs can also function in the opposite role as guidance cues to alter axon behavior. Furthermore, the data support a model in which dorsal retinal ganglion cell axons heading to the optic disc encounter a gradient of inhibitory EphB proteins which helps maintain tight axon fasciculation and prevents aberrant axon growth into ventral retina. In conclusion, development of neuronal connectivity may involve the combined activity of Eph proteins serving as guidance receptors and as axon guidance cues.

scholarly journals CRMP2 and CRMP4 Are Differentially Required for Axon Guidance and Growth in Zebrafish Retinal Neurons

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Zhi-Zhi Liu ◽  
Jian Zhu ◽  
Chang-Ling Wang ◽  
Xin Wang ◽  
Ying-Ying Han ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Retinal Ganglion ◽  
Guidance Cues ◽  
Retinal Axons ◽  
Neuropilin 1 ◽  
Axon Development ◽  
Intracellular Proteins ◽  
Retinal Axon

Axons are directed to their correct targets by guidance cues during neurodevelopment. Many axon guidance cues have been discovered; however, much less known is about how the growth cones transduce the extracellular guidance cues to intracellular responses. Collapsin response mediator proteins (CRMPs) are a family of intracellular proteins that have been found to mediate growth cone behavior in vitro; however, their roles in vivo in axon development are much less explored. In zebrafish embryos, we find that CRMP2 and CRMP4 are expressed in the retinal ganglion cell layer when retinal axons are crossing the midline. Knocking down CRMP2 causes reduced elongation and premature termination of the retinal axons, while knocking down CRMP4 results in ipsilateral misprojections of retinal axons that would normally project to the contralateral brain. Furthermore, CRMP4 synchronizes with neuropilin 1 in retinal axon guidance, suggesting that CRMP4 might mediate the semaphorin/neuropilin signaling pathway. These results demonstrate that CRMP2 and CRMP4 function differentially in axon development in vivo.

scholarly journals Polycaprolactone/Gelatin/Hyaluronic Acid Electrospun Scaffolds to Mimic Glioblastoma Extracellular Matrix

Materials ◽  
2020 ◽  
Vol 13 (11) ◽  
pp. 2661 ◽  
Author(s):  
Semra Unal ◽  
Sema Arslan ◽  
Betul Karademir Yilmaz ◽  
Faik Nuzhet Oktar ◽  
Denisa Ficai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Rotational Velocity ◽  
Axon Growth ◽  
Scanning Calorimetry ◽  
Composite Scaffolds ◽  
Water Contact ◽  
Human Brain Tumor ◽  
Novel Therapeutic Strategies

Glioblastoma (GBM), one of the most malignant types of human brain tumor, is resistant to conventional treatments and is associated with poor survival. Since the 3D extracellular matrix (ECM) of GBM microenvironment plays a significant role on the tumor behavior, the engineering of the ECM will help us to get more information on the tumor behavior and to define novel therapeutic strategies. In this study, polycaprolactone (PCL)/gelatin(Gel)/hyaluronic acid(HA) composite scaffolds with aligned and randomly oriented nanofibers were successfully fabricated by electrospinning for mimicking the extracellular matrix of GBM tumor. We investigated the effect of nanotopography and components of fibers on the mechanical, morphological, and hydrophilic properties of electrospun nanofiber as well as their biocompatibility properties. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) have been used to investigate possible interactions between components. The mean fiber diameter in the nanofiber matrix was increased with the presence of HA at low collector rotation speed. Moreover, the rotational velocity of the collector affected the fiber diameters as well as their homogenous distribution. Water contact angle measurements confirmed that hyaluronic acid-incorporated aligned nanofibers were more hydrophilic than that of random nanofibers. In addition, PCL/Gel/HA nanofibrous scaffold (7.9 MPa) exhibited a significant decrease in tensile strength compared to PCL/Gel nanofibrous mat (19.2 MPa). In-vitro biocompatibilities of nanofiber scaffolds were tested with glioblastoma cells (U251), and the PCL/Gel/HA scaffolds with random nanofiber showed improved cell adhesion and proliferation. On the other hand, PCL/Gel/HA scaffolds with aligned nanofiber were found suitable for enhancing axon growth and elongation supporting intracellular communication. Based on these results, PCL/Gel/HA composite scaffolds are excellent candidates as a biomimetic matrix for GBM and the study of the tumor.

Vascularisation for cardiac tissue engineering: the extracellular matrix

2015 ◽  
Vol 113 (03) ◽  
pp. 532-547 ◽  
Author(s):  
Chinmoy Patra ◽  
Aldo Boccaccini ◽  
Felix Engel
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Cardiac Tissue ◽  
Heart Diseases ◽  
Cardiac Tissue Engineering ◽  
Promising Candidate ◽  
Realistic Option ◽  
Extracellular Matrix Molecules ◽  
Heart Muscle Cells

SummaryCardiovascular diseases present a major socio-economic burden. One major problem underlying most cardiovascular and congenital heart diseases is the irreversible loss of contractile heart muscle cells, the cardiomyocytes. To reverse damage incurred by myocardial infarction or by surgical correction of cardiac malformations, the loss of cardiac tissue with a thickness of a few millimetres needs to be compensated. A promising approach to this issue is cardiac tissue engineering. In this review we focus on the problem of in vitro vascularisation as implantation of cardiac patches consisting of more than three layers of cardiomyocytes (> 100 μm thick) already results in necrosis. We explain the need for vascularisation and elaborate on the importance to include non-myocytes in order to generate functional vascularised cardiac tissue. We discuss the potential of extracellular matrix molecules in promoting vascularisation and introduce nephronectin as an example of a new promising candidate. Finally, we discuss current biomaterial- based approaches including micropatterning, electrospinning, 3D micro-manufacturing technology and porogens. Collectively, the current literature supports the notion that cardiac tissue engineering is a realistic option for future treatment of paediatric and adult patients with cardiac disease.

scholarly journals Nell2 regulates the contralateral-versus-ipsilateral visual projection as a layer-specific positional cue

2018 ◽  
Author(s):  
Chizu Nakamoto ◽  
Elaine Durward ◽  
Masato Horie ◽  
Masaru Nakamoto
Keyword(s):  
Axon Guidance ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Retinal Ganglion ◽  
Guidance Cue ◽  
Retinal Axons ◽  
Visual Projection ◽  
Summary Statement ◽  
Retinogeniculate Projection ◽  
Dorsal Lateral Geniculate

SUMMARY STATEMENTNell2 is an ipsilateral layer-specific axon guidance cue in the visual thalamus and contributes to establishment of the eye-specific retinogeniculate projection by specifically inhibiting contralateral retinal axons.ABSTRACTIn mammals with binocular vision, retinal ganglion cell (RGC) axons from each eye project to eye-specific layers in the contralateral and ipsilateral dorsal lateral geniculate nucleus (dLGN). Although layer-specific axon guidance cues that discriminate contralateral and ipsilateral RGC axons have long been postulated as a key mechanism for development of the eye-specificretinogeniculate projection, the molecular nature of such cues has remained elusive. Here we show that the extracellular glycoprotein Nell2 (also known as Nel) is expressed in the dorsomedial region of the dLGN, which corresponds to the layer receiving ipsilateral RGC axons. In Nell2 mutant mice, contralateral RGC axons invaded the ipsilateral layer of the dLGN, and ipsilateral axons terminated in partially fragmented patches, forming a mosaic pattern of contralateral and ipsilateral axon termination zones. In vitro, Nell2 exerted inhibitory effects on contralateral, but not ipsilateral, RGC axons. These results provide evidence that Nell2 acts as a layer-specific positional label in the dLGN that discriminates contralateral and ipsilateral RGC axons, and that it plays essential roles in establishment of the eye-specific projection patterns in the retinogeniculate system.

scholarly journals Pax6 modulates intra-retinal axon guidance and fasciculation of retinal ganglion cells during retinogenesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Soundararajan Lalitha ◽  
Budhaditya Basu ◽  
Suresh Surya ◽  
Vadakkath Meera ◽  
Paul Ann Riya ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Ganglion Cells ◽  
Transcriptome Profiling ◽  
Retinal Ganglion ◽  
Temporal Expression ◽  
Fate Specification ◽  
Extracellular Matrix Molecules ◽  
Coordinated Expression ◽  
Spatio Temporal ◽  
Retinal Axon

Abstract Intra-retinal axon guidance involves a coordinated expression of transcription factors, axon guidance genes, and secretory molecules within the retina. Pax6, the master regulator gene, has a spatio-temporal expression typically restricted till neurogenesis and fate-specification. However, our observation of persistent expression of Pax6 in mature RGCs led us to hypothesize that Pax6 could play a major role in axon guidance after fate specification. Here, we found significant alteration in intra-retinal axon guidance and fasciculation upon knocking out of Pax6 in E15.5 retina. Through unbiased transcriptome profiling between Pax6fl/fl and Pax6−/− retinas, we revealed the mechanistic insight of its role in axon guidance. Our results showed a significant increase in the expression of extracellular matrix molecules and decreased expression of retinal fate specification and neuron projection guidance molecules. Additionally, we found that EphB1 and Sema5B are directly regulated by Pax6 owing to the guidance defects and improper fasciculation of axons. We conclude that Pax6 expression post fate specification of RGCs is necessary for regulating the expression of axon guidance genes and most importantly for maintaining a conducive ECM through which the nascent axons get guided and fasciculate to reach the optic disc.

Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 19-30 ◽  
Author(s):  
M. Placzek ◽  
M. Tessier-Lavigne ◽  
T. Jessell ◽  
J. Dodd
Keyword(s):  
Spinal Cord ◽  
Collagen Gel ◽  
Axon Growth ◽  
Local Environment ◽  
Floor Plate ◽  
Target Cells ◽  
Commissural Axon ◽  
Commissural Axons ◽  
Commissural Neurons

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are short-range, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.

scholarly journals Topographically Specific Effects of ELF-1 on Retinal Axon Guidance In Vitro and Retinal Axon Mapping In Vivo

Cell ◽  
1996 ◽  
Vol 86 (5) ◽  
pp. 755-766 ◽  
Author(s):  
Masaru Nakamoto ◽  
Hwai-Jong Cheng ◽  
Glenn C Friedman ◽  
Todd McLaughlin ◽  
Michael J Hansen ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Specific Effects ◽  
Retinal Axon
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