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 α1, 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.
We are grateful to Andy Furley, Steve Winder and Jeffrey Miner for providing us with antibodies, and Raquel Andrade for designing primers. We thank members of the Borycki and Thorsteinsdottir labs for their comments and support, especially F. Bajanca for helpful discussions. We thank Chris Hill at the electron microscopy facility, Jeremy Sanderson at the light microscopy facility, and Lynne Williams, Stevie O'Keefe and Rachael Ivatt for their technical support. The light microscopy facility is supported by a grant from the Wellcome Trust(GR077544AIA). This work was supported by grants from the European Commission Sixth Framework Programme (Cells into Organs contract: LSHM-CT-2003-504468) to A.G.B. and S.T., and (MYORES contract: 511978) to A.G.B. Deposited in PMC for release after 6 months.
