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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.

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Distribution of  laminin α1 and α5 chains in  embryonic and extraembryonic BLs. Sections of embryos at the indicated ages  were labeled with antibodies  specific for the laminin α1,  α5, or γ1 chains. The γ1 chain  is present in, and thus serves  to mark, all BLs. (A–C) BLs  underlying the unclosed neuroepithelium (n), the surface  ectoderm (se), and the gut epithelium (g) contain both α1  and α5 chains at E8.7. (D–F)  After neural tube closure, α5  levels decrease in the neuroepithelial BL, and α1 levels  decrease in the surface ectodermal BL. (G–I) By E13.5,  α5 is confined to the BL adjacent to the floorplate of the  spinal cord (sc) (arrow in H)  and to the notochord (nc),  whereas α1 is found throughout the pial BL but is absent  from the notochord. Neither  chain is present in BLs of  blood vessels within and outside the spinal cord. These  vascular BLs contain laminin  α4 (not shown). (J–L) In  E10.5 heart, both α1 and α5  are found in the atria (a) and  in the ventricles (v), though  levels of α1 are low in ventricle. (M–O) In the nascent  placental labyrinth, the BLs  at the base of embryonic  blood vessels in the ectoplacental plate (epp) contain  both α1 and α5, whereas the  tips of vessels that have migrated towards the maternal  blood spaces (arrowheads)  contain α5 but lack α1. N and  O are from a single, doubly  labeled section. (P–R) In  E13.5 placental labyrinth,  the fetal blood vessel BLs  contain both α1 and α5  throughout their lengths.  Bar, 10 μm for A–C and P–R,  20 μm for all other panels.
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Figure 1: Distribution of laminin α1 and α5 chains in embryonic and extraembryonic BLs. Sections of embryos at the indicated ages were labeled with antibodies specific for the laminin α1, α5, or γ1 chains. The γ1 chain is present in, and thus serves to mark, all BLs. (A–C) BLs underlying the unclosed neuroepithelium (n), the surface ectoderm (se), and the gut epithelium (g) contain both α1 and α5 chains at E8.7. (D–F) After neural tube closure, α5 levels decrease in the neuroepithelial BL, and α1 levels decrease in the surface ectodermal BL. (G–I) By E13.5, α5 is confined to the BL adjacent to the floorplate of the spinal cord (sc) (arrow in H) and to the notochord (nc), whereas α1 is found throughout the pial BL but is absent from the notochord. Neither chain is present in BLs of blood vessels within and outside the spinal cord. These vascular BLs contain laminin α4 (not shown). (J–L) In E10.5 heart, both α1 and α5 are found in the atria (a) and in the ventricles (v), though levels of α1 are low in ventricle. (M–O) In the nascent placental labyrinth, the BLs at the base of embryonic blood vessels in the ectoplacental plate (epp) contain both α1 and α5, whereas the tips of vessels that have migrated towards the maternal blood spaces (arrowheads) contain α5 but lack α1. N and O are from a single, doubly labeled section. (P–R) In E13.5 placental labyrinth, the fetal blood vessel BLs contain both α1 and α5 throughout their lengths. Bar, 10 μm for A–C and P–R, 20 μm for all other panels.

Mentions: Laminin α5 was present in virtually all γ1-positive BLs at embryonic day (E) 8.5 (Fig. 1, A and B). These included the BL underlying the neural folds and the surface ectoderm, as well as BLs associated with gut epithelium. Thus, laminin α5 is not only a major α chain in adult BLs (Miner et al., 1997) but also a prominent component of BLs at early somite stages. At later stages, however, the distribution of α5 became restricted to a subset of BLs. In the spinal cord, for example, α5 was found throughout the pial BL at E9.5 (Fig. 1 E), but levels then decreased in dorsal regions, and by E13.5, this chain was confined to the floorplate at the ventral midline (Fig. 1 H). On the other hand, α5 remained abundant in the surface ectodermal BL throughout embryogenesis (Fig. 1 and data not shown).


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)

Distribution of  laminin α1 and α5 chains in  embryonic and extraembryonic BLs. Sections of embryos at the indicated ages  were labeled with antibodies  specific for the laminin α1,  α5, or γ1 chains. The γ1 chain  is present in, and thus serves  to mark, all BLs. (A–C) BLs  underlying the unclosed neuroepithelium (n), the surface  ectoderm (se), and the gut epithelium (g) contain both α1  and α5 chains at E8.7. (D–F)  After neural tube closure, α5  levels decrease in the neuroepithelial BL, and α1 levels  decrease in the surface ectodermal BL. (G–I) By E13.5,  α5 is confined to the BL adjacent to the floorplate of the  spinal cord (sc) (arrow in H)  and to the notochord (nc),  whereas α1 is found throughout the pial BL but is absent  from the notochord. Neither  chain is present in BLs of  blood vessels within and outside the spinal cord. These  vascular BLs contain laminin  α4 (not shown). (J–L) In  E10.5 heart, both α1 and α5  are found in the atria (a) and  in the ventricles (v), though  levels of α1 are low in ventricle. (M–O) In the nascent  placental labyrinth, the BLs  at the base of embryonic  blood vessels in the ectoplacental plate (epp) contain  both α1 and α5, whereas the  tips of vessels that have migrated towards the maternal  blood spaces (arrowheads)  contain α5 but lack α1. N and  O are from a single, doubly  labeled section. (P–R) In  E13.5 placental labyrinth,  the fetal blood vessel BLs  contain both α1 and α5  throughout their lengths.  Bar, 10 μm for A–C and P–R,  20 μm for all other panels.
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Related In: Results  -  Collection

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Figure 1: Distribution of laminin α1 and α5 chains in embryonic and extraembryonic BLs. Sections of embryos at the indicated ages were labeled with antibodies specific for the laminin α1, α5, or γ1 chains. The γ1 chain is present in, and thus serves to mark, all BLs. (A–C) BLs underlying the unclosed neuroepithelium (n), the surface ectoderm (se), and the gut epithelium (g) contain both α1 and α5 chains at E8.7. (D–F) After neural tube closure, α5 levels decrease in the neuroepithelial BL, and α1 levels decrease in the surface ectodermal BL. (G–I) By E13.5, α5 is confined to the BL adjacent to the floorplate of the spinal cord (sc) (arrow in H) and to the notochord (nc), whereas α1 is found throughout the pial BL but is absent from the notochord. Neither chain is present in BLs of blood vessels within and outside the spinal cord. These vascular BLs contain laminin α4 (not shown). (J–L) In E10.5 heart, both α1 and α5 are found in the atria (a) and in the ventricles (v), though levels of α1 are low in ventricle. (M–O) In the nascent placental labyrinth, the BLs at the base of embryonic blood vessels in the ectoplacental plate (epp) contain both α1 and α5, whereas the tips of vessels that have migrated towards the maternal blood spaces (arrowheads) contain α5 but lack α1. N and O are from a single, doubly labeled section. (P–R) In E13.5 placental labyrinth, the fetal blood vessel BLs contain both α1 and α5 throughout their lengths. Bar, 10 μm for A–C and P–R, 20 μm for all other panels.
Mentions: Laminin α5 was present in virtually all γ1-positive BLs at embryonic day (E) 8.5 (Fig. 1, A and B). These included the BL underlying the neural folds and the surface ectoderm, as well as BLs associated with gut epithelium. Thus, laminin α5 is not only a major α chain in adult BLs (Miner et al., 1997) but also a prominent component of BLs at early somite stages. At later stages, however, the distribution of α5 became restricted to a subset of BLs. In the spinal cord, for example, α5 was found throughout the pial BL at E9.5 (Fig. 1 E), but levels then decreased in dorsal regions, and by E13.5, this chain was confined to the floorplate at the ventral midline (Fig. 1 H). On the other hand, α5 remained abundant in the surface ectodermal BL throughout embryogenesis (Fig. 1 and data not shown).

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