Limits...
Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain.

Miner JH, Cunningham J, Sanes JR - J. Cell Biol. (1998)

Bottom Line: Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development.Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate.Our results identify new roles for laminins and BLs in diverse developmental processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Renal Division, St. Louis, Missouri, USA.

ABSTRACT
Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin alpha5 chain is required during embryogenesis. The alpha5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose alpha5 retain or acquire other alpha chains. Embryos lacking laminin alpha5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are alpha5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.

Show MeSH

Related in: MedlinePlus

Electron micrographs of epithelial BLs in the heads of  control (B–E) and mutant (F–I) embryos at E8.7. (A) Drawing  indicating the approximate origins of the sections shown in B–I.  The narrow line represents the BL. (B and F) Lateral cranial surface ectoderm. (C and G) Surface ectoderm near the dorsal midline. (D and H) Junction of surface ectoderm and neuroepithelium. (E and I) Neuroepithelium. BLs are intact in both mutants  and controls beneath lateral ectoderm and neuroepithelium. BLs  are discontinuous in both mutants and controls near the junction  of ectoderm and neuroepithelium. Beneath the surface ectoderm  near the neural folds, however, control BL is intact, whereas mutant BL is disrupted. This region of the ectoderm has been shown  to be important in neural tube closure (see text). n, neuroepithelium; se, surface ectoderm; arrowheads, BL. Bar, 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2132973&req=5

Figure 6: Electron micrographs of epithelial BLs in the heads of control (B–E) and mutant (F–I) embryos at E8.7. (A) Drawing indicating the approximate origins of the sections shown in B–I. The narrow line represents the BL. (B and F) Lateral cranial surface ectoderm. (C and G) Surface ectoderm near the dorsal midline. (D and H) Junction of surface ectoderm and neuroepithelium. (E and I) Neuroepithelium. BLs are intact in both mutants and controls beneath lateral ectoderm and neuroepithelium. BLs are discontinuous in both mutants and controls near the junction of ectoderm and neuroepithelium. Beneath the surface ectoderm near the neural folds, however, control BL is intact, whereas mutant BL is disrupted. This region of the ectoderm has been shown to be important in neural tube closure (see text). n, neuroepithelium; se, surface ectoderm; arrowheads, BL. Bar, 0.5 μm.

Mentions: In control embryos, the basal surfaces of the ectoderm and neuroectoderm were coated by a continuous BL, but discontinuities were apparent at the junction of ectoderm and neuroectoderm, the area through which neural crest cells later migrate from the dorsal neural tube to the periphery (Fig. 6, B–E). The mutant BL was similar to that of controls in being continuous beneath the neuroectoderm and ectoderm but discontinuous at the ectodermal–neuroectodermal junction (Fig. 6, F, H, and I). Lama5 −/− ectodermal BL differed from that of controls, however, along a strip bordering the neural folds: the ectodermal BL of controls was continuous, whereas that of mutants was thin and patchy (Fig. 6 G). This difference was seen in several mutant/control littermate pairs. Interestingly, Schoenwolf and colleagues have suggested that this strip of ectoderm is involved in generating forces that are necessary to close the neural tube (Schoenwolf and Smith, 1990; Hackett et al., 1997). We speculate that weakness of the BL in this region decreases the amount of lateral force the ectoderm can generate on the neural folds, thereby leading to sporadic failure of cranial neural tube closure.


Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain.

Miner JH, Cunningham J, Sanes JR - J. Cell Biol. (1998)

Electron micrographs of epithelial BLs in the heads of  control (B–E) and mutant (F–I) embryos at E8.7. (A) Drawing  indicating the approximate origins of the sections shown in B–I.  The narrow line represents the BL. (B and F) Lateral cranial surface ectoderm. (C and G) Surface ectoderm near the dorsal midline. (D and H) Junction of surface ectoderm and neuroepithelium. (E and I) Neuroepithelium. BLs are intact in both mutants  and controls beneath lateral ectoderm and neuroepithelium. BLs  are discontinuous in both mutants and controls near the junction  of ectoderm and neuroepithelium. Beneath the surface ectoderm  near the neural folds, however, control BL is intact, whereas mutant BL is disrupted. This region of the ectoderm has been shown  to be important in neural tube closure (see text). n, neuroepithelium; se, surface ectoderm; arrowheads, BL. Bar, 0.5 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132973&req=5

Figure 6: Electron micrographs of epithelial BLs in the heads of control (B–E) and mutant (F–I) embryos at E8.7. (A) Drawing indicating the approximate origins of the sections shown in B–I. The narrow line represents the BL. (B and F) Lateral cranial surface ectoderm. (C and G) Surface ectoderm near the dorsal midline. (D and H) Junction of surface ectoderm and neuroepithelium. (E and I) Neuroepithelium. BLs are intact in both mutants and controls beneath lateral ectoderm and neuroepithelium. BLs are discontinuous in both mutants and controls near the junction of ectoderm and neuroepithelium. Beneath the surface ectoderm near the neural folds, however, control BL is intact, whereas mutant BL is disrupted. This region of the ectoderm has been shown to be important in neural tube closure (see text). n, neuroepithelium; se, surface ectoderm; arrowheads, BL. Bar, 0.5 μm.
Mentions: In control embryos, the basal surfaces of the ectoderm and neuroectoderm were coated by a continuous BL, but discontinuities were apparent at the junction of ectoderm and neuroectoderm, the area through which neural crest cells later migrate from the dorsal neural tube to the periphery (Fig. 6, B–E). The mutant BL was similar to that of controls in being continuous beneath the neuroectoderm and ectoderm but discontinuous at the ectodermal–neuroectodermal junction (Fig. 6, F, H, and I). Lama5 −/− ectodermal BL differed from that of controls, however, along a strip bordering the neural folds: the ectodermal BL of controls was continuous, whereas that of mutants was thin and patchy (Fig. 6 G). This difference was seen in several mutant/control littermate pairs. Interestingly, Schoenwolf and colleagues have suggested that this strip of ectoderm is involved in generating forces that are necessary to close the neural tube (Schoenwolf and Smith, 1990; Hackett et al., 1997). We speculate that weakness of the BL in this region decreases the amount of lateral force the ectoderm can generate on the neural folds, thereby leading to sporadic failure of cranial neural tube closure.

Bottom Line: Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development.Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate.Our results identify new roles for laminins and BLs in diverse developmental processes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Renal Division, St. Louis, Missouri, USA.

ABSTRACT
Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are alpha/beta/gamma heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin alpha5 chain is required during embryogenesis. The alpha5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose alpha5 retain or acquire other alpha chains. Embryos lacking laminin alpha5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are alpha5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin alpha chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.

Show MeSH
Related in: MedlinePlus