(A-H) Wnt1-Cre mediated ablation of Shp2 in the neural crest resulted in the complete loss of Shp2 staining within the periocular mesenchyme (C and D, arrows). This consequently lead to the abrogation of the lacrimal gland buds that are normally present at E14.5 (A-D, dotted lines). The lacrimal gland primordia in Shp2 mutants still expressed Pax6 and E-cadherin (E-F, dotted lines), but failed to upregulate Col1a1 expression (G-H, dotted lines). (I-R) At E13.5, Fgf10 is normally expressed in the periocular mesenchyme to induce pERK, Etv4 and Etv5 in the lacrimal gland bud, but these downstream targets were all down regulated in the Shp2 mutants. Arrow: Fgf10 expression near to the future lacrimal gland bud. Arrowhead: Fgf10 expression in the eyelid mesenchyme. The lacrimal gland primordia were outlined with dotted lines.