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This place of worship was erected in the X century thanks to the financial contributions of the Capello and Zane families. It was initially dedicated to St Christina as there was a nearby convent dedicated to the Saint, and only after did the title of the church change to Santa Maria Mater Domini. The first church tower was built in 1384 by Marco Cappello, a second in 1503 and it was then further altered due to its sudden collapse in 1740. The first construction of the church evoked the typical byzantine style with three aisles (the lateral ones were lower); this composition persisted even though the successive alterations until the Fifteenth century. In the early years of the XVI century it was razed to the ground and was completely rebuilt: we are not completely sure which architect oversaw the project but recent studies attribute it to Mauro Codussi. The works went on until at least 1542 and the official consecration took place on the 25th of July 1540 by Lucio Bishop of Sebenico. This new religious building was designed in a typical Renaissance style, with a Greek cross plan and a cupola at the intersection of the transept. Large stone pillars support the arches and delimit the main nave and the four side chapels. Next to the presbytery and apse are two smaller niche chapels.

The external facade is made of grey stone and not adorned. The lower order exhibits Corinthian pillars and a simple portal, while the upper section is reserved for a Rose window.

Inside are works by: Vincenzo Catena with the Martyrdom of St Christina, Jacopo Tintoretto with the Discovering the True Cross and Francesco Bissolo with the Transfiguration. You can also admire masterpieces of the Venetian School, such as the statue of the Madonna Praying, and the Tuscan School. The statues inside are nearly all by Lorenzo Bregno.

By decree of the Council of Ten on the 24th of April 1488 — due to a series of occurrences of sodomy and dishonesty — the portico of the church, which had been used to carry out such immoral activities, was closed with boards, secured at the gate and locked with a bolt at midnight.

The palace next to the church, in Campo Santa Maria Mater Domini, belong to the Zane dynasty, as shown in the family arms depicting a fox engraved on the wellhead in the internal courtyard of the building; it is said that in 1310 this residence was branded with the Lion of St Mark, as one of the owners had participated in the conspiracy against the Serenissima, organised by Bajamonte Tiepolo.

Nearby you can also see the arms of the Cappello family who once lived in the area (the palace was then knocked down) along with that of one of the brothers, Bartolomeo Cappello, who had moved to St Apollinare upon marriage and later fathered Bianca Cappello, the famous noblewoman who was crowned Grand Duchess of Tuscany in 1579. Furthermore, near the the bridge of Santa Maria Mater Domini lived the two literary brothers Gasparo and Carlo Gozzi, who wrote at length in their memoirs about the house built by the family in 1550.

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