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The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance.

Ackley BD, Crew JR, Elamaa H, Pihlajaniemi T, Kuo CJ, Kramer JM - J. Cell Biol. (2001)

Bottom Line: The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system.In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain.These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

ABSTRACT
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

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Related in: MedlinePlus

Localization of CLE-1 and type IV collagen in wild-type and cg120 animals. Immunofluorescent localization of CLE-1 (A–H) and type IV collagen (I and J) are shown in wild-type (A–D and I) and cg120 (E–H and J) animals. In all panels, anterior is left, and dorsal is up. (A) A fourfold embryo shows strong CLE-1 staining associated with the nerve ring (arrowhead). (B) In larval animals, CLE-1 accumulates on the nerve ring (arrowhead) and the dorsal (dc) and ventral (vc) nerve cords. (C) In adults, staining for CLE-1 is strong on the nerve ring and nerve cords (dc and vc) and is weakly detected on the surfaces of the pharynx (p), intestine (i), and gonad (g). (D) Under body wall muscle of an adult, CLE-1 accumulates strongly at the junctions between muscle cells (arrowheads) and along muscle-dense body lines (small arrows) but is not coincident with the dense bodies. Staining on the ventral nerve cord is distinctly punctate. (E) Weak CLE-1 accumulation on the nerve ring of a cg120 embryo. (F) CLE-1 localization to the nerve ring (arrowhead) and dorsal (dc) and ventral (vc) nerve cords of a cg120 larva. (G) Accumulation on nerve ring (arrowhead), nerve cords (dc and vc), pharynx (p), and intestine (i) of a cg120 adult. (H) Under the body wall muscle of a cg120 adult, CLE-1 accumulates along dense body lines (small arrows) and along the ventral nerve cord (vc) as in wild type. However, there is no accumulation at the junctions between muscle cells (arrowheads), and the pattern on the nerve cord is more diffuse. (I and J) Wild-type and cg120 L1 larvae show type IV collagen localization in the basement membranes of the pharynx (p), intestine (i), and gonad primordium (g).
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Figure 3: Localization of CLE-1 and type IV collagen in wild-type and cg120 animals. Immunofluorescent localization of CLE-1 (A–H) and type IV collagen (I and J) are shown in wild-type (A–D and I) and cg120 (E–H and J) animals. In all panels, anterior is left, and dorsal is up. (A) A fourfold embryo shows strong CLE-1 staining associated with the nerve ring (arrowhead). (B) In larval animals, CLE-1 accumulates on the nerve ring (arrowhead) and the dorsal (dc) and ventral (vc) nerve cords. (C) In adults, staining for CLE-1 is strong on the nerve ring and nerve cords (dc and vc) and is weakly detected on the surfaces of the pharynx (p), intestine (i), and gonad (g). (D) Under body wall muscle of an adult, CLE-1 accumulates strongly at the junctions between muscle cells (arrowheads) and along muscle-dense body lines (small arrows) but is not coincident with the dense bodies. Staining on the ventral nerve cord is distinctly punctate. (E) Weak CLE-1 accumulation on the nerve ring of a cg120 embryo. (F) CLE-1 localization to the nerve ring (arrowhead) and dorsal (dc) and ventral (vc) nerve cords of a cg120 larva. (G) Accumulation on nerve ring (arrowhead), nerve cords (dc and vc), pharynx (p), and intestine (i) of a cg120 adult. (H) Under the body wall muscle of a cg120 adult, CLE-1 accumulates along dense body lines (small arrows) and along the ventral nerve cord (vc) as in wild type. However, there is no accumulation at the junctions between muscle cells (arrowheads), and the pattern on the nerve cord is more diffuse. (I and J) Wild-type and cg120 L1 larvae show type IV collagen localization in the basement membranes of the pharynx (p), intestine (i), and gonad primordium (g).

Mentions: Anti–CLE-1 antiserum was raised against a region common to all isoforms and used to localize the protein in whole animals. CLE-1 strongly accumulates in a punctate pattern associated with the nerve ring and the dorsal and ventral nerve cords. This pattern is first visible at the twofold stage of embryogenesis (∼460 min) and persists in all subsequent stages (Fig. 3). Beginning in the L4 larval stage, CLE-1 is also observed in basement membranes surrounding the gonad, pharynx, and intestine (Fig. 3 C), and under body wall muscles where it preferentially accumulates at junctions between muscle cells and along dense body lines (Fig. 3 D). The apparently more limited distribution of CLE-1 in early development may result from low sensitivity of detection with the antibody.


The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance.

Ackley BD, Crew JR, Elamaa H, Pihlajaniemi T, Kuo CJ, Kramer JM - J. Cell Biol. (2001)

Localization of CLE-1 and type IV collagen in wild-type and cg120 animals. Immunofluorescent localization of CLE-1 (A–H) and type IV collagen (I and J) are shown in wild-type (A–D and I) and cg120 (E–H and J) animals. In all panels, anterior is left, and dorsal is up. (A) A fourfold embryo shows strong CLE-1 staining associated with the nerve ring (arrowhead). (B) In larval animals, CLE-1 accumulates on the nerve ring (arrowhead) and the dorsal (dc) and ventral (vc) nerve cords. (C) In adults, staining for CLE-1 is strong on the nerve ring and nerve cords (dc and vc) and is weakly detected on the surfaces of the pharynx (p), intestine (i), and gonad (g). (D) Under body wall muscle of an adult, CLE-1 accumulates strongly at the junctions between muscle cells (arrowheads) and along muscle-dense body lines (small arrows) but is not coincident with the dense bodies. Staining on the ventral nerve cord is distinctly punctate. (E) Weak CLE-1 accumulation on the nerve ring of a cg120 embryo. (F) CLE-1 localization to the nerve ring (arrowhead) and dorsal (dc) and ventral (vc) nerve cords of a cg120 larva. (G) Accumulation on nerve ring (arrowhead), nerve cords (dc and vc), pharynx (p), and intestine (i) of a cg120 adult. (H) Under the body wall muscle of a cg120 adult, CLE-1 accumulates along dense body lines (small arrows) and along the ventral nerve cord (vc) as in wild type. However, there is no accumulation at the junctions between muscle cells (arrowheads), and the pattern on the nerve cord is more diffuse. (I and J) Wild-type and cg120 L1 larvae show type IV collagen localization in the basement membranes of the pharynx (p), intestine (i), and gonad primordium (g).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199198&req=5

Figure 3: Localization of CLE-1 and type IV collagen in wild-type and cg120 animals. Immunofluorescent localization of CLE-1 (A–H) and type IV collagen (I and J) are shown in wild-type (A–D and I) and cg120 (E–H and J) animals. In all panels, anterior is left, and dorsal is up. (A) A fourfold embryo shows strong CLE-1 staining associated with the nerve ring (arrowhead). (B) In larval animals, CLE-1 accumulates on the nerve ring (arrowhead) and the dorsal (dc) and ventral (vc) nerve cords. (C) In adults, staining for CLE-1 is strong on the nerve ring and nerve cords (dc and vc) and is weakly detected on the surfaces of the pharynx (p), intestine (i), and gonad (g). (D) Under body wall muscle of an adult, CLE-1 accumulates strongly at the junctions between muscle cells (arrowheads) and along muscle-dense body lines (small arrows) but is not coincident with the dense bodies. Staining on the ventral nerve cord is distinctly punctate. (E) Weak CLE-1 accumulation on the nerve ring of a cg120 embryo. (F) CLE-1 localization to the nerve ring (arrowhead) and dorsal (dc) and ventral (vc) nerve cords of a cg120 larva. (G) Accumulation on nerve ring (arrowhead), nerve cords (dc and vc), pharynx (p), and intestine (i) of a cg120 adult. (H) Under the body wall muscle of a cg120 adult, CLE-1 accumulates along dense body lines (small arrows) and along the ventral nerve cord (vc) as in wild type. However, there is no accumulation at the junctions between muscle cells (arrowheads), and the pattern on the nerve cord is more diffuse. (I and J) Wild-type and cg120 L1 larvae show type IV collagen localization in the basement membranes of the pharynx (p), intestine (i), and gonad primordium (g).
Mentions: Anti–CLE-1 antiserum was raised against a region common to all isoforms and used to localize the protein in whole animals. CLE-1 strongly accumulates in a punctate pattern associated with the nerve ring and the dorsal and ventral nerve cords. This pattern is first visible at the twofold stage of embryogenesis (∼460 min) and persists in all subsequent stages (Fig. 3). Beginning in the L4 larval stage, CLE-1 is also observed in basement membranes surrounding the gonad, pharynx, and intestine (Fig. 3 C), and under body wall muscles where it preferentially accumulates at junctions between muscle cells and along dense body lines (Fig. 3 D). The apparently more limited distribution of CLE-1 in early development may result from low sensitivity of detection with the antibody.

Bottom Line: The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system.In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain.These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.

ABSTRACT
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

Show MeSH
Related in: MedlinePlus