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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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Expression patterns of cle-1::GFP transcriptional reporters. Isoform-specific GFP transcriptional reporters show the expression patterns of cle-1A (A and E), cle-1B (B and F), and cle-1C (C, D, G, and H). In A–D, anterior is up and dorsal is to the left; in E–H, anterior is to the left, and dorsal is up. (A) cle-1A expression in the cephalic neurons of a 1.75-fold stage embryo. Expression is also seen in S-type interneurons at later stages. (B) cle-1B expression in a threefold embryo is seen in DD ventral motorneurons (four are visible and two are out of the plane of focus). This GFP fusion localizes to the nucleus, making axon visualization difficult. (C) cle-1C expression in the body wall muscles (bm) of a twofold embryo. Pharyngeal expression is not seen in this focal plane. (D) In a threefold embryo, cle-1C expression in body wall muscles is weaker, but strong expression is seen in pharyngeal cells (p), accessory muscles, some unidentified cells near the anus (a), and the canal-associated neurons (CAN). (E) In an L2 larva, cle-1A expression is strong in the nerve ring (nr) and rectal epithelial cells (re). GFP is weakly detected in axons of the S-type interneurons that run sublaterally. (F) cle-1B expression in dorsal motorneuron cell bodies (arrowheads) located along the ventral nerve cord of an L2 larva. Faint GFP activity can be detected in commissural axons of most animals. (G) cle-1C expression in an L2 larva is limited to a subset of glial-like GLR cells, the head mesodermal cell (hm), the canal-associated neurons, and weakly in the anal sphincter muscle (sm). (H) cle-1C expression in adult body wall muscles (bm), accessory muscles (sm), canal associated neurons (CAN), and gonadal sheath cells (sc).
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Figure 2: Expression patterns of cle-1::GFP transcriptional reporters. Isoform-specific GFP transcriptional reporters show the expression patterns of cle-1A (A and E), cle-1B (B and F), and cle-1C (C, D, G, and H). In A–D, anterior is up and dorsal is to the left; in E–H, anterior is to the left, and dorsal is up. (A) cle-1A expression in the cephalic neurons of a 1.75-fold stage embryo. Expression is also seen in S-type interneurons at later stages. (B) cle-1B expression in a threefold embryo is seen in DD ventral motorneurons (four are visible and two are out of the plane of focus). This GFP fusion localizes to the nucleus, making axon visualization difficult. (C) cle-1C expression in the body wall muscles (bm) of a twofold embryo. Pharyngeal expression is not seen in this focal plane. (D) In a threefold embryo, cle-1C expression in body wall muscles is weaker, but strong expression is seen in pharyngeal cells (p), accessory muscles, some unidentified cells near the anus (a), and the canal-associated neurons (CAN). (E) In an L2 larva, cle-1A expression is strong in the nerve ring (nr) and rectal epithelial cells (re). GFP is weakly detected in axons of the S-type interneurons that run sublaterally. (F) cle-1B expression in dorsal motorneuron cell bodies (arrowheads) located along the ventral nerve cord of an L2 larva. Faint GFP activity can be detected in commissural axons of most animals. (G) cle-1C expression in an L2 larva is limited to a subset of glial-like GLR cells, the head mesodermal cell (hm), the canal-associated neurons, and weakly in the anal sphincter muscle (sm). (H) cle-1C expression in adult body wall muscles (bm), accessory muscles (sm), canal associated neurons (CAN), and gonadal sheath cells (sc).

Mentions: cle-1 expression was analyzed in transgenic animals carrying GFP transcriptional reporters driven by sequences upstream of the unique first exon of each isoform. cle-1A::GFP expression was first detected in comma stage (∼390 min) embryos in cephalic neurons (Fig. 2 A). Expression in interneurons and rectal epithelial cells is seen by the twofold stage, ∼60 min later, and continues through larval and adult stages (Fig. 2 E). cle-1B::GFP expression was first observed at the threefold stage (∼520 min) of embryogenesis in four neurons of the lateral ganglia and in the DD dorsal motorneurons (Fig. 2 B). The postembryonic VD dorsal motorneurons also express cle-1B::GFP starting in the second larval stage, and this pattern persists through larval and adult stages (Fig. 2 F).


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)

Expression patterns of cle-1::GFP transcriptional reporters. Isoform-specific GFP transcriptional reporters show the expression patterns of cle-1A (A and E), cle-1B (B and F), and cle-1C (C, D, G, and H). In A–D, anterior is up and dorsal is to the left; in E–H, anterior is to the left, and dorsal is up. (A) cle-1A expression in the cephalic neurons of a 1.75-fold stage embryo. Expression is also seen in S-type interneurons at later stages. (B) cle-1B expression in a threefold embryo is seen in DD ventral motorneurons (four are visible and two are out of the plane of focus). This GFP fusion localizes to the nucleus, making axon visualization difficult. (C) cle-1C expression in the body wall muscles (bm) of a twofold embryo. Pharyngeal expression is not seen in this focal plane. (D) In a threefold embryo, cle-1C expression in body wall muscles is weaker, but strong expression is seen in pharyngeal cells (p), accessory muscles, some unidentified cells near the anus (a), and the canal-associated neurons (CAN). (E) In an L2 larva, cle-1A expression is strong in the nerve ring (nr) and rectal epithelial cells (re). GFP is weakly detected in axons of the S-type interneurons that run sublaterally. (F) cle-1B expression in dorsal motorneuron cell bodies (arrowheads) located along the ventral nerve cord of an L2 larva. Faint GFP activity can be detected in commissural axons of most animals. (G) cle-1C expression in an L2 larva is limited to a subset of glial-like GLR cells, the head mesodermal cell (hm), the canal-associated neurons, and weakly in the anal sphincter muscle (sm). (H) cle-1C expression in adult body wall muscles (bm), accessory muscles (sm), canal associated neurons (CAN), and gonadal sheath cells (sc).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Expression patterns of cle-1::GFP transcriptional reporters. Isoform-specific GFP transcriptional reporters show the expression patterns of cle-1A (A and E), cle-1B (B and F), and cle-1C (C, D, G, and H). In A–D, anterior is up and dorsal is to the left; in E–H, anterior is to the left, and dorsal is up. (A) cle-1A expression in the cephalic neurons of a 1.75-fold stage embryo. Expression is also seen in S-type interneurons at later stages. (B) cle-1B expression in a threefold embryo is seen in DD ventral motorneurons (four are visible and two are out of the plane of focus). This GFP fusion localizes to the nucleus, making axon visualization difficult. (C) cle-1C expression in the body wall muscles (bm) of a twofold embryo. Pharyngeal expression is not seen in this focal plane. (D) In a threefold embryo, cle-1C expression in body wall muscles is weaker, but strong expression is seen in pharyngeal cells (p), accessory muscles, some unidentified cells near the anus (a), and the canal-associated neurons (CAN). (E) In an L2 larva, cle-1A expression is strong in the nerve ring (nr) and rectal epithelial cells (re). GFP is weakly detected in axons of the S-type interneurons that run sublaterally. (F) cle-1B expression in dorsal motorneuron cell bodies (arrowheads) located along the ventral nerve cord of an L2 larva. Faint GFP activity can be detected in commissural axons of most animals. (G) cle-1C expression in an L2 larva is limited to a subset of glial-like GLR cells, the head mesodermal cell (hm), the canal-associated neurons, and weakly in the anal sphincter muscle (sm). (H) cle-1C expression in adult body wall muscles (bm), accessory muscles (sm), canal associated neurons (CAN), and gonadal sheath cells (sc).
Mentions: cle-1 expression was analyzed in transgenic animals carrying GFP transcriptional reporters driven by sequences upstream of the unique first exon of each isoform. cle-1A::GFP expression was first detected in comma stage (∼390 min) embryos in cephalic neurons (Fig. 2 A). Expression in interneurons and rectal epithelial cells is seen by the twofold stage, ∼60 min later, and continues through larval and adult stages (Fig. 2 E). cle-1B::GFP expression was first observed at the threefold stage (∼520 min) of embryogenesis in four neurons of the lateral ganglia and in the DD dorsal motorneurons (Fig. 2 B). The postembryonic VD dorsal motorneurons also express cle-1B::GFP starting in the second larval stage, and this pattern persists through larval and adult stages (Fig. 2 F).

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