Sonic hedgehog-dependent synthesis of laminin alpha1 controls basement membrane assembly in the myotome.
Basement membranes have essential structural and signalling roles in tissue morphogenesis during embryonic development, but the mechanisms that control their formation are still poorly understood. Laminins are key components of basement membranes and are thought to be essential for initiation of basement membrane assembly. Here, we report that muscle progenitor cells populating the myotome migrate aberrantly in the ventral somite in the absence of sonic hedgehog (Shh) signalling, and we show that this defect is due to the failure to form a myotomal basement membrane. We reveal that expression of Lama1, which encodes laminin alpha1, a subunit of laminin-111, is not activated in Shh(-/-) embryos. Recovery of Lama1 expression or addition of exogenous laminin-111 to Shh(-/-);Gli3(-/-) embryos restores the myotomal basement membrane, demonstrating that laminin-111 is necessary and sufficient to initiate assembly of the myotomal basement membrane. This study uncovers an essential role for Shh signalling in the control of laminin-111 synthesis and in the initiation of basement membrane assembly in the myotome. Furthermore, our data indicate that laminin-111 function cannot be compensated by laminin-511.
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Claire
C
Anderson
Sólveig
S
Thorsteinsdóttir
Anne-Gaëlle
AG
Borycki
D000818:Animals; D001485:Basement Membrane / Q000196:embryology* / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D039121:Integrin alpha6beta1 / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D024510:Muscle Development; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism* / Q000648:ultrastructure; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
C498520:Gli1 protein, mouse; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D039121:Integrin alpha6beta1; D051741:Kruppel-Like Transcription Factors; D007797:Laminin; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D009419:Nerve Tissue Proteins; C465570:Shh protein, mouse; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; C084098:laminin A