Limits...
Perlecan maintains the integrity of cartilage and some basement membranes.

Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R - J. Cell Biol. (1999)

Bottom Line: As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function.The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly.Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden.

ABSTRACT
Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

Show MeSH

Related in: MedlinePlus

Development of the hemopericard in E10.5 perlecan- embryos. (A and B) Whole mount pictures of E10.5 wild-type (A) and perlecan-deficient embryos showing blood leakage into the pericardial cavity (B, arrow). (C–H) Light microscopy of semi-thin sections of wild-type (C and E) and perlecan- hearts (D and F–H) stained with methylene blue. (C) Myocardial wall with well developed trabeculation separated from the thin pericardium by a cell-free cavity. (E) Higher magnification shows that cardiomyocytes are covered by an endo- and epicardial cell layer. (D) Myocardial wall of homozygotes is disrupted (arrow), whereas the endo- and epicardial cell layers are intact. The pericardial cavity contains blood cells and is surrounded by a thickened pericardium. (F–H) Three different perlecan- hearts with small ruptures in the myocardial wall (arrows). (I–K) Electron microscopy of a normal (I) cardiac muscle cell with BM composed of a lamina rara and densa (arrow). Mutant cardiac muscle cell shows a typical myofilament organization but lacks a BM (arrow in J) or with BM-like material (arrow in K) on the cell surface. (L and M) Typical BM with a lamina rara and densa (arrow) beneath the dermal epithelium of wild-type (L) and perlecan- (M) embryos. (N-Q) Immunostaining for perlecan (N and O) and laminin-1 (P and Q) of a wild-type (N and P) and perlecan- (O and Q) heart. Perlecan is absent but laminin-1 is expressed in homozygous hearts. Abbreviations: v, ventricle; m, myocardium; p, pericardium; mf, muscle filament; and e, epithelial cell. Bars: (C and D) 250 μm; (E–H) 100 μm; (I–M) 250 nm; and (N–Q) 250 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2169352&req=5

Figure 2: Development of the hemopericard in E10.5 perlecan- embryos. (A and B) Whole mount pictures of E10.5 wild-type (A) and perlecan-deficient embryos showing blood leakage into the pericardial cavity (B, arrow). (C–H) Light microscopy of semi-thin sections of wild-type (C and E) and perlecan- hearts (D and F–H) stained with methylene blue. (C) Myocardial wall with well developed trabeculation separated from the thin pericardium by a cell-free cavity. (E) Higher magnification shows that cardiomyocytes are covered by an endo- and epicardial cell layer. (D) Myocardial wall of homozygotes is disrupted (arrow), whereas the endo- and epicardial cell layers are intact. The pericardial cavity contains blood cells and is surrounded by a thickened pericardium. (F–H) Three different perlecan- hearts with small ruptures in the myocardial wall (arrows). (I–K) Electron microscopy of a normal (I) cardiac muscle cell with BM composed of a lamina rara and densa (arrow). Mutant cardiac muscle cell shows a typical myofilament organization but lacks a BM (arrow in J) or with BM-like material (arrow in K) on the cell surface. (L and M) Typical BM with a lamina rara and densa (arrow) beneath the dermal epithelium of wild-type (L) and perlecan- (M) embryos. (N-Q) Immunostaining for perlecan (N and O) and laminin-1 (P and Q) of a wild-type (N and P) and perlecan- (O and Q) heart. Perlecan is absent but laminin-1 is expressed in homozygous hearts. Abbreviations: v, ventricle; m, myocardium; p, pericardium; mf, muscle filament; and e, epithelial cell. Bars: (C and D) 250 μm; (E–H) 100 μm; (I–M) 250 nm; and (N–Q) 250 μm.

Mentions: By E10.5, defects began to appear in perlecan- embryos. Although they were still present in the expected percentage (Table ) and were of normal size, ∼70–80% were dead as demonstrated by the absence of the heart beating and the presence of severe hemopericardium (Fig. 2 B, arrow). 20–30% of homozygotes were alive and of normal appearance (not shown). By E11.5 and E12.5 the percentage of dead embryos with hemopericardium increased further, whereas some of the living embryos developed abnormally in the head region and survived to the perinatal period. At all stages analyzed, the placental development was unaffected by the loss of perlecan. The placental size, architecture, and the blood content were similar between normal and perlecan- embryos (not shown). In addition, PECAM whole mount stainings of E9.5 and E10.5 embryos revealed that homozygotes had no defects in angiogenesis, sprouting, and remodeling to generate vessels of different sizes (not shown). At later stages of development (E13–E17), we could observe the formation of microaneurysms associated with bleedings in several tissues including lung, skin, and brain (not shown).


Perlecan maintains the integrity of cartilage and some basement membranes.

Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fässler R - J. Cell Biol. (1999)

Development of the hemopericard in E10.5 perlecan- embryos. (A and B) Whole mount pictures of E10.5 wild-type (A) and perlecan-deficient embryos showing blood leakage into the pericardial cavity (B, arrow). (C–H) Light microscopy of semi-thin sections of wild-type (C and E) and perlecan- hearts (D and F–H) stained with methylene blue. (C) Myocardial wall with well developed trabeculation separated from the thin pericardium by a cell-free cavity. (E) Higher magnification shows that cardiomyocytes are covered by an endo- and epicardial cell layer. (D) Myocardial wall of homozygotes is disrupted (arrow), whereas the endo- and epicardial cell layers are intact. The pericardial cavity contains blood cells and is surrounded by a thickened pericardium. (F–H) Three different perlecan- hearts with small ruptures in the myocardial wall (arrows). (I–K) Electron microscopy of a normal (I) cardiac muscle cell with BM composed of a lamina rara and densa (arrow). Mutant cardiac muscle cell shows a typical myofilament organization but lacks a BM (arrow in J) or with BM-like material (arrow in K) on the cell surface. (L and M) Typical BM with a lamina rara and densa (arrow) beneath the dermal epithelium of wild-type (L) and perlecan- (M) embryos. (N-Q) Immunostaining for perlecan (N and O) and laminin-1 (P and Q) of a wild-type (N and P) and perlecan- (O and Q) heart. Perlecan is absent but laminin-1 is expressed in homozygous hearts. Abbreviations: v, ventricle; m, myocardium; p, pericardium; mf, muscle filament; and e, epithelial cell. Bars: (C and D) 250 μm; (E–H) 100 μm; (I–M) 250 nm; and (N–Q) 250 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169352&req=5

Figure 2: Development of the hemopericard in E10.5 perlecan- embryos. (A and B) Whole mount pictures of E10.5 wild-type (A) and perlecan-deficient embryos showing blood leakage into the pericardial cavity (B, arrow). (C–H) Light microscopy of semi-thin sections of wild-type (C and E) and perlecan- hearts (D and F–H) stained with methylene blue. (C) Myocardial wall with well developed trabeculation separated from the thin pericardium by a cell-free cavity. (E) Higher magnification shows that cardiomyocytes are covered by an endo- and epicardial cell layer. (D) Myocardial wall of homozygotes is disrupted (arrow), whereas the endo- and epicardial cell layers are intact. The pericardial cavity contains blood cells and is surrounded by a thickened pericardium. (F–H) Three different perlecan- hearts with small ruptures in the myocardial wall (arrows). (I–K) Electron microscopy of a normal (I) cardiac muscle cell with BM composed of a lamina rara and densa (arrow). Mutant cardiac muscle cell shows a typical myofilament organization but lacks a BM (arrow in J) or with BM-like material (arrow in K) on the cell surface. (L and M) Typical BM with a lamina rara and densa (arrow) beneath the dermal epithelium of wild-type (L) and perlecan- (M) embryos. (N-Q) Immunostaining for perlecan (N and O) and laminin-1 (P and Q) of a wild-type (N and P) and perlecan- (O and Q) heart. Perlecan is absent but laminin-1 is expressed in homozygous hearts. Abbreviations: v, ventricle; m, myocardium; p, pericardium; mf, muscle filament; and e, epithelial cell. Bars: (C and D) 250 μm; (E–H) 100 μm; (I–M) 250 nm; and (N–Q) 250 μm.
Mentions: By E10.5, defects began to appear in perlecan- embryos. Although they were still present in the expected percentage (Table ) and were of normal size, ∼70–80% were dead as demonstrated by the absence of the heart beating and the presence of severe hemopericardium (Fig. 2 B, arrow). 20–30% of homozygotes were alive and of normal appearance (not shown). By E11.5 and E12.5 the percentage of dead embryos with hemopericardium increased further, whereas some of the living embryos developed abnormally in the head region and survived to the perinatal period. At all stages analyzed, the placental development was unaffected by the loss of perlecan. The placental size, architecture, and the blood content were similar between normal and perlecan- embryos (not shown). In addition, PECAM whole mount stainings of E9.5 and E10.5 embryos revealed that homozygotes had no defects in angiogenesis, sprouting, and remodeling to generate vessels of different sizes (not shown). At later stages of development (E13–E17), we could observe the formation of microaneurysms associated with bleedings in several tissues including lung, skin, and brain (not shown).

Bottom Line: As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function.The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly.Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Pathology, Lund University, S-221 85 Lund, Sweden.

ABSTRACT
Perlecan is a heparan sulfate proteoglycan that is expressed in all basement membranes (BMs), in cartilage, and several other mesenchymal tissues during development. Perlecan binds growth factors and interacts with various extracellular matrix proteins and cell adhesion molecules. Homozygous mice with a mutation in the perlecan gene exhibit normal formation of BMs. However, BMs deteriorate in regions with increased mechanical stress such as the contracting myocardium and the expanding brain vesicles showing that perlecan is crucial for maintaining BM integrity. As a consequence, small clefts are formed in the cardiac muscle leading to blood leakage into the pericardial cavity and an arrest of heart function. The defects in the BM separating the brain from the adjacent mesenchyme caused invasion of brain tissue into the overlaying ectoderm leading to abnormal expansion of neuroepithelium, neuronal ectopias, and exencephaly. Finally, homozygotes developed a severe defect in cartilage, a tissue that lacks BMs. The chondrodysplasia is characterized by a reduction of the fibrillar collagen network, shortened collagen fibers, and elevated expression of cartilage extracellular matrix genes, suggesting that perlecan protects cartilage extracellular matrix from degradation.

Show MeSH
Related in: MedlinePlus