scholarly journals Slit-Robo Signalling Establishes a Sphingosine-1-Phosphate Gradient to Polarise Fin Mesenchyme and Establish Fin Morphology

2021 ◽  
Author(s):  
Harsha Mahabaleshwar ◽  
P.V. Asharani ◽  
Tricia Loo Yi Jun ◽  
Shze Yung Koh ◽  
Melissa R. Pitman ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Positional Cloning ◽  
Gene Encoding ◽  
Apical Domain ◽  
Limb Morphogenesis ◽  
Robo Receptors ◽  
Tensile Forces ◽  
Sphingosine 1 Phosphate ◽  
Mesenchyme Cell ◽  
Mesenchyme Cells

SUMMARYImmigration of mesenchymal cells into the growing fin and limb buds drives distal outgrowth, with subsequent tensile forces between these cells essential for fin and limb morphogenesis. Morphogens derived from the apical domain of the fin, orientate limb mesenchyme cell polarity, migration, division and adhesion. The zebrafish mutant stomp displays defects in fin morphogenesis including blister formation and associated loss of orientation and adhesion of immigrating fin mesenchyme cells. Positional cloning of stomp identified a mutation in the gene encoding the axon guidance ligand, Slit3. We provide evidence that Slit ligands derived from immigrating mesenchyme act via Robo receptors at the Apical Ectodermal Ridge (AER) to promote release of sphingosine-1-phosphate (S1P). S1P subsequently diffuses back to the mesenchyme to promote their polarisation, orientation, positioning and adhesion to the interstitial matrix of the fin fold. We thus demonstrate coordination of the Slit-Robo and S1P signalling pathways in fin fold morphogenesis. Our work introduces a mechanism regulating the orientation, positioning and adhesion of its constituent cells.

Early embryonic expression ofFGF4/6/9gene and its role in the induction of mesenchyme and notochord inCiona savignyiembryos

Development ◽  
2002 ◽  
Vol 129 (7) ◽  
pp. 1729-1738 ◽  
Author(s):  
Kaoru S. Imai ◽  
Nori Satoh ◽  
Yutaka Satou
Keyword(s):  
Cell Differentiation ◽  
Nuclear Localization ◽  
Target Genes ◽  
Muscle Cells ◽  
Cell Stage ◽  
Ciona Savignyi ◽  
Mesenchyme Cell ◽  
Notochord Cells ◽  
Mesenchyme Cells ◽  
Endodermal Cells

In early Ciona savignyi embryos, nuclear localization of β-catenin is the first step of endodermal cell specification, and triggers the activation of various target genes. A cDNA for Cs-FGF4/6/9, a gene activated downstream of β-catenin signaling, was isolated and shown to encode an FGF protein with features of both FGF4/6 and FGF9/20. The early embryonic expression of Cs-FGF4/6/9 was transient and the transcript was seen in endodermal cells at the 16- and 32-cell stages, in notochord and muscle cells at the 64-cell stage, and in nerve cord and muscle cells at the 110-cell stage; the gene was then expressed again in cells of the nervous system after neurulation. When the gene function was suppressed with a specific antisense morpholino oligo, the differentiation of mesenchyme cells was completely blocked, and the fate of presumptive mesenchyme cells appeared to change into that of muscle cells. The inhibition of mesenchyme differentiation was abrogated by coinjection of the morpholino oligo and synthetic Cs-FGF4/6/9 mRNA. Downregulation of β-catenin nuclear localization resulted in the absence of mesenchyme cell differentiation due to failure of the formation of signal-producing endodermal cells. Injection of synthetic Cs-FGF4/6/9 mRNA in β-catenin-downregulated embryos evoked mesenchyme cell differentiation. These results strongly suggest that Cs-FGF4/6/9 produced by endodermal cells acts an inductive signal for the differentiation of mesenchyme cells. On the other hand, the role of Cs-FGF4/6/9 in the induction of notochord cells is partial; the initial process of the induction was inhibited by Cs-FGF4/6/9 morpholino oligo, but notochord-specific genes were expressed later to form a partial notochord.

Scanning electron microscopy of gastrulation in a sea urchin (Anthocidaris crassispina)

Development ◽  
1982 ◽  
Vol 67 (1) ◽  
pp. 27-35
Author(s):  
Shonan Amemiya ◽  
Koji Akasaka ◽  
Hiroshi Terayama
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Cell Formation ◽  
Cell Movement ◽  
Animal Pole ◽  
Vegetal Pole ◽  
Mesenchyme Cell ◽  
Major Motive ◽  
Mesenchyme Cells ◽  
Scanning Electron

Gastrulation in Anthocidaris was investigated by observing the inside and the outside of embryos by scanning electron microscopy. Furrows which possibly rėflect changes in intercellular interactions were observed on the outer surface (hyaline layer side) of embryos twice in development: firstly at the time of primary mesenchyme cell formation, and secondly at the time of vegetal plate indentation. In the latter case, the cells within and surrounding the vegetal plate appeared to change their shapes differently; the former (within the plate) having broader surfaces on the blastocoel side whereas the latter (surrounding the plate) having broader surfaces on the hyaline layer side. This suggests that the first phase of indentation may be mediated by the autonomous change of cell shape and intercellular adhesiveness, accompanied by an autonomous cell movement in the vegetal pole region. Although some pseudopodial linkages were observed between secondary mesenchyme cells on the top of the invaginating archenteron and the animal pole in the mid-gastrula and later stage embryos, they were thinner and smaller in number as compared to those in the Pseudocentrotus embryos. The rate of invagination appeared rather constant throughout gastrulation in contrast to the accelerated invagination in other embryos with larger blastocoel cavities. Moreover, the number of columnar cells on the dissected surface of embryos remained unaltered. These findings suggest that the secondary mesenchyme cells may act as a linker between the archenteron tip and the animal pole, but they may not generate major motive forces for archenteron invagination at least in the Anthocidaris embryos.

scholarly journals Morphogenesis of the islets of Langerhans is guided by extra-endocrine Slit2/3 signals

2020 ◽  
pp. MCB.00451-20
Author(s):  
Jennifer M. Gilbert ◽  
Melissa T. Adams ◽  
Nadav Sharon ◽  
Hariharan Jayaraaman ◽  
Barak Blum
Keyword(s):  
Axon Guidance ◽  
Islets Of Langerhans ◽  
Endocrine Cells ◽  
Β Cells ◽  
Robo Receptors ◽  
Correct Function ◽  
Cell Positioning ◽  
Spatial Architecture ◽  
Endocrine Tissues

The spatial architecture of the islets of Langerhans is vitally important for their correct function, and alterations in islet morphogenesis often result in diabetes mellitus. We have previously reported that Roundabout (Robo) receptors are required for proper islet morphogenesis. As part of the Slit-Robo signaling pathway, Robo receptors function in conjunction with Slit ligands to mediate axon guidance, cell migration, and cell positioning in development. However, the role of Slit ligands in islet morphogenesis has not yet been determined. Here we report that Slit ligands are expressed in overlapping and distinct patterns in both endocrine and non-endocrine tissues in late pancreas development. We show that function of either Slit2 or Slit3, which are predominantly expressed in the pancreatic mesenchyme, is required and sufficient for islet morphogenesis, while Slit1, which is predominantly expressed in the β-cells, is dispensable for islet morphogenesis. We further show that Slit functions as a repellent signal to β-cells. These data suggest that clustering of endocrine cells during islet morphogenesis is guided, at least in part, by repelling Slit2/3 signals from the pancreatic mesenchyme.

scholarly journals Role of fibronectin in primary mesenchyme cell migration in the sea urchin.

1985 ◽  
Vol 101 (4) ◽  
pp. 1487-1491 ◽  
Author(s):  
H Katow ◽  
M Hayashi
Keyword(s):  
Cell Migration ◽  
Sea Urchin ◽  
Culture Media ◽  
Horse Serum ◽  
Time Lapse ◽  
Mesenchyme Cell ◽  
Mesenchyme Cells ◽  
Primary Mesenchyme Cells

We studied the effect of fibronectin (FN) on the behavior of primary mesenchyme cells isolated from sea urchin mesenchyme blastulae in vitro using a time-lapse technique. The migration of isolated primary mesenchyme cells reconstituted in seawater and horse serum is dependent on the presence or absence of exogenous FN in the culture media. The cells in FN, 4 and 40 micrograms/ml, show a high percentage of migration and migrate long distances, whereas a higher concentration of FN at 400 micrograms/ml tends to inhibit migration.

scholarly journals Minimal structural elements required for midline repulsive signaling and regulation of Drosophila Robo1

2020 ◽  
Author(s):  
Haley E. Brown ◽  
Timothy A. Evans
Keyword(s):  
Axon Guidance ◽  
Biochemical Properties ◽  
Structural Elements ◽  
Wild Type ◽  
Domain Interaction ◽  
Robo Receptors ◽  
Guidance Receptors ◽  
Repulsive Signaling

AbstractThe Roundabout (Robo) family of axon guidance receptors has a conserved ectodomain arrangement of five immunoglobulin-like (Ig) domains plus three fibronectin (Fn) repeats. Based on the strong evolutionary conservation of this domain structure among Robo receptors, as well as in vitro structural and domain-domain interaction studies of Robo family members, this ectodomain arrangement is predicted to be important for Robo receptor signaling in response to Slit ligands. Here, we define the minimal ectodomain structure required for Slit binding and midline repulsive signaling in vivo by Drosophila Robo1. We find that the majority of the Robo1 ectodomain is dispensable for both Slit binding and repulsive signaling. We show that a significant level of midline repulsive signaling activity is retained when all Robo1 ectodomain elements apart from Ig1 are deleted, and that the combination of Ig1 plus one additional ectodomain element (Ig2, Ig5, or Fn3) is sufficient to restore midline repulsion to wild type levels. Further, we find that deleting four out of five Robo1 Ig domains (ΔIg2-5) does not affect negative regulation of Robo1 by Commissureless (Comm) or Robo2, while variants lacking all three fibronectin repeats (ΔFn1-3 and ΔIg2-Fn3) are insensitive to regulation by both Comm and Robo2, signifying a novel regulatory role for Robo1’s Fn repeats. Our results provide an in vivo perspective on the importance of the conserved 5+3 ectodomain structure of Robo receptors, and suggest that specific biochemical properties and/or ectodomain structural conformations observed in vitro for domains other than Ig1 may have limited significance for in vivo signaling in the context of midline repulsion.

scholarly journals Lateral neuron–glia interactions steer the response of axons to the Robo code

2004 ◽  
Vol 1 (2) ◽  
pp. 101-112 ◽  
Author(s):  
EDWARD F.V. KINRADE ◽  
ALICIA HIDALGO
Keyword(s):  
Axon Guidance ◽  
Glial Cells ◽  
Double Mutant ◽  
Ectopic Expression ◽  
Axon Pathfinding ◽  
Longitudinal Trajectories ◽  
Robo Receptors ◽  
Lateral Positioning

Glia are required for axon pathfinding along longitudinal trajectories, but it is unknown how this relates to the molecular paradigm of axon guidance across the midline. Most interneuron axons in bilateral organisms cross the midline only once. Preventing them from recrossing the midline requires the expression of Robo receptors on the axons. These sense the repulsive signal Slit, which is produced by the midline. The lateral positioning of longitudinal axons depends on the response to Slit by the combination of Robo receptors expressed by the axons, on selective fasciculation, and on longitudinal (lateral) glia. Here, we analyse how longitudinal glia influence reading of the ‘Robo code’ by axons. We show that whereas loss of robo1 alone only affects the most medial axons, loss of both glial cells missing (gcm) and robo1 causes a severe midline collapse of longitudinal axons, similar to that caused by the loss of multiple Robo receptors. Furthermore, whereas ectopic expression of robo2 is sufficient to displace the medial MP2 axons along a more lateral trajectory, this does not occur in gcm–robo1 double-mutant embryos, where axons either do not extend at all or they misroute exiting the CNS. Hence, lateral neuron–glia interactions steer the response of axons to the Robo code.

scholarly journals Targeting the SLIT/ROBO pathway in tumor progression: molecular mechanisms and therapeutic perspectives

2019 ◽  
Vol 11 ◽  
pp. 175883591985523 ◽  
Author(s):  
Zhengdong Jiang ◽  
Gang Liang ◽  
Ying Xiao ◽  
Tao Qin ◽  
Xin Chen ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Tumor Development ◽  
Tumor Promotion ◽  
Cancer Therapies ◽  
Malignant Cells ◽  
Robo Receptors

The SLITs (SLIT1, SLIT2, and SLIT3) are a family of secreted proteins that mediate positional interactions between cells and their environment during development by signaling through ROBO receptors (ROBO1, ROBO2, ROBO3, and ROBO4). The SLIT/ROBO signaling pathway has been shown to participate in axonal repulsion, axon guidance, and neuronal migration in the nervous system and the formation of the vascular system. However, the role of the SLIT/ROBO pathway has not been thoroughly clarified in tumor development. The SLIT/ROBO pathway can produce both beneficial and detrimental effects in the growth of malignant cells. It has been confirmed that SLIT/ROBO play contradictory roles in tumorigenesis. Here, we discuss the tumor promotion and tumor suppression roles of the SLIT/ROBO pathway in tumor growth, angiogenesis, migration, and the tumor microenvironment. Understanding these roles will help us develop more effective cancer therapies.

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