A model describing the mechanism of Mmp1 and Mmp2 function during CCM of CBs.

<p>(A) In wildtype stage 16 embryos visualised in cross-section, Mmp2 is targeted to the LE where it cleaves components of the ECM, allowing for stabilisation of a Cadherin domain, and releasing embedded morphogens, possibly Slit, which trigger filopodia and lamellopodia formation. Mmp1 is targeted to the preluminal domain, where it excludes assembly of Cadherin-based adherens junctions and partakes in homeostatic ECM turnover. Pericardin localization is limited to the basal side of the CBs. (B) In <i>mmp1</i> loss-of-function embryos, Pericardin is present at a reduced luminal ECM, suggesting Mmp1 negatively regulates the size of the Cadherin domain and Pericardin deposition. Mmp2 is likely targeted to the LE where it degrades ECM components and releases embedded morphogens. (C) In <i>mmp2</i> loss of function embryos, the apical identity of both junctional and preluminal domain is disrupted suggesting Mmp2 is essential for Integrin and Slit mediated CB polarization.