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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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Related in: MedlinePlus

Syndactyly in Lama5 −/− embryos. Controls are on the  left and mutants on the right. (A and B) Whole mount dorsal  views of E14.5 fore- and hindlimbs. Digits 1 and 5 are partially  septated in the mutant hindlimb. (C and D) Alcian blue staining  at E13.5 demonstrates proper patterning in the mutant. Digits 2  and 3 are closely apposed but are not fused (arrows). (E and F)  Alcian blue staining at E15.5 shows complete fusion of mutant  digits 2 and 3 (arrows) and the absence of distal phalanges from  digits 2–4 in the mutant forelimb.
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Figure 3: Syndactyly in Lama5 −/− embryos. Controls are on the left and mutants on the right. (A and B) Whole mount dorsal views of E14.5 fore- and hindlimbs. Digits 1 and 5 are partially septated in the mutant hindlimb. (C and D) Alcian blue staining at E13.5 demonstrates proper patterning in the mutant. Digits 2 and 3 are closely apposed but are not fused (arrows). (E and F) Alcian blue staining at E15.5 shows complete fusion of mutant digits 2 and 3 (arrows) and the absence of distal phalanges from digits 2–4 in the mutant forelimb.

Mentions: In normal mice, distal extremities of limbs are initially paddle-shaped, then septation occurs to form digits. The distal limbs of Lama5 −/− embryos were also initially paddle-shaped, but then became club-like and failed to form separate digits, a phenomenon known as syndactyly. This defect was visible at E12.5, as soon as septation began in controls. It became more obvious at later ages and was apparent in all Lama5 −/− mice examined (Fig. 3, A and B). The forelimbs were more severely affected than the hindlimbs; little if any septation occurred in mutant forelimbs, but digits 1 and 5 exhibited partial separation in hindlimbs by E14.5.


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)

Syndactyly in Lama5 −/− embryos. Controls are on the  left and mutants on the right. (A and B) Whole mount dorsal  views of E14.5 fore- and hindlimbs. Digits 1 and 5 are partially  septated in the mutant hindlimb. (C and D) Alcian blue staining  at E13.5 demonstrates proper patterning in the mutant. Digits 2  and 3 are closely apposed but are not fused (arrows). (E and F)  Alcian blue staining at E15.5 shows complete fusion of mutant  digits 2 and 3 (arrows) and the absence of distal phalanges from  digits 2–4 in the mutant forelimb.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Syndactyly in Lama5 −/− embryos. Controls are on the left and mutants on the right. (A and B) Whole mount dorsal views of E14.5 fore- and hindlimbs. Digits 1 and 5 are partially septated in the mutant hindlimb. (C and D) Alcian blue staining at E13.5 demonstrates proper patterning in the mutant. Digits 2 and 3 are closely apposed but are not fused (arrows). (E and F) Alcian blue staining at E15.5 shows complete fusion of mutant digits 2 and 3 (arrows) and the absence of distal phalanges from digits 2–4 in the mutant forelimb.
Mentions: In normal mice, distal extremities of limbs are initially paddle-shaped, then septation occurs to form digits. The distal limbs of Lama5 −/− embryos were also initially paddle-shaped, but then became club-like and failed to form separate digits, a phenomenon known as syndactyly. This defect was visible at E12.5, as soon as septation began in controls. It became more obvious at later ages and was apparent in all Lama5 −/− mice examined (Fig. 3, A and B). The forelimbs were more severely affected than the hindlimbs; little if any septation occurred in mutant forelimbs, but digits 1 and 5 exhibited partial separation in hindlimbs by E14.5.

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