Temporal delay of molar tooth development in Barx1 homozygous mutants. Hematoxylin and eosin stained frontal (A–J) and sagittal (K and L) sections of lower E13.5 incisors (A and B) and first molars (C and D), E14.5 incisors (E and F), and first molars (G and H), E16.5 first molars (I and J), and postnatal day 0 (P0) first molars (K and L). At E13.5, all tooth germs have reached a bud stage both in the Barx1 homozygous mutant (B and D) and control littermate (A and C). Incisors develop normally in all Barx1 homozygous mutants, displaying a characteristic epithelial cap at E14.5 (E and F), whereas the molars of all four quadrants show a developmental delay between E13.5 and E14.5, exhibiting a bud shape instead of a cap (G and H) (n > 10). Arrowheads in E–G indicate the primary enamel knot, visualized as a bulge on the inside of the epithelial cap. At E16.5–P0, Barx1−/− molars are slightly smaller but otherwise normal (I–L). m, Meckel's cartilage; vl, vestibular lamina. (Scale bar, 100 μm in A–J and 200 μm in K and L.)