Fig. 4

Defects seen in zebrafish and chicken embryos following thalidomide analog treatment A. Embryos with exposure to a vehicle control show normal development of the eye (e), and B. pectoral fins (pf). Example of an anti-angiogenic compound (C4, Figure 1) causing C. microopthalmia (white arrow; seen in list the compounds) and D. malformation in fin development (white arrow). Exposure to an anti-inflammatory compound (C2, Figure 1) resulting in E. normal eye development and F. fin development. G. Eye diameter and H. fin length were quantified and show anti-angiogenic compounds causing reductions in eye diameter (C4, C18, C82, C83, C84) and pectoral fin length (C18, C81, C82). Compounds of interest were screened in chicken embryos at HH stage 17-18 (Day 2.5 in embryonic development). I. Untreated, control images of an embryo in ovo with normal vascular patterns at HH stage 23 (Day 3.5); K. ex ovo; M. eye O. forelimb and Q. hindlimb showing cartilage patterning (at day 9 of development). Typical examples of compound treated embryos: J. anomaly in vasculature (white arrow) and necrosis (black arrow) of the YSM in a chicken embryo following treatment with C23 (Supplementary Table S1). L. embryo exhibiting microopthalmia (asterix), limb reduction (white arrow) and hemorrhaging throughout the body following treatment with C80 and (N) C81 (Figure 1) treated embryo with growth reduction and hemorrhaging throughout head (white arrow). P. C11 treated limb with reduced elements (Asterisks represents a limb reduction defect). R. Missing digits and reduced length of limb cartilage elements (Treated with C11, Supplementary Table S1). Scale bar represents 1000 µm.