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Botticelli’s lunette fresco of the Nativity in the nave of Santa Maria Novella depicts a moment shortly after the birth of the Christ child. The Virgin Mary, Christ, and Joseph occupy the center of a dilapidated stone structure. The ox and ass are seen through a hole in the stone wall, and in front of them, the Christ child gestures toward the Virgin Mary who kneels in prayer. A young St. John the Baptist appears behind Mary holding a cross. Joseph sits to the right with his head in his hand, contemplating the miracle of the birth of Christ.
In Nativity scenes, the ox represents those who accept the Christian faith, while the ass symbolizes those who deny: Jews, Muslims, and pagans.
Lightbown, Ronald. Sandro Botticelli: Life and Work (vol. 2). Berkeley: University of California Press, 1978. Pg. 32-33.