Axolotl pronephric duct migration requires an epidermally derived, laminin 1-containing extracellular matrix and the integrin receptor 61

The epidermis overlying the migrating axolotl pronephric duct is known to participate in duct guidance. This epidermis deposits an extracellular matrix onto the migrating duct and its pathway that is a potential source of directional guidance cues. The role of this matrix in pronephric duct guidance was assayed by presenting matrix deposited on microcarriers directly to migrating pronephric ducts in situ. We found that reorientation of extracellular-matrix-bearing carriers prior to their presentation to migrating ducts caused a corresponding reorientation of pronephric duct migration. Subepidermal microinjection of function-blocking antibodies against 6 integrin, 1 integrin or the laminin-1/E8 domain recognized by 61 integrin, all of which were detected and localized here, inhibited pronephric duct migration. Moreover, pre-exposure to anti-laminin-1/E8 function-blocking antibody prevented reoriented carriers of epidermally deposited matrix from reorienting pronephric duct migration. These results are incorporated into an integrated model of pronephric duct guidance consistent with all present evidence, proposing roles for the previously implicated glial cell-line derived neurotrophic factor and its receptor as well as for laminin 1 and 61 integrin.