Conversation so far:
Was Isabella I of Castile married?
Isabella and her husband had created an empire.
Where was the empire located?
CANNOTANSWER.
Do they have any kids?
Isabella's plans for her eldest two children did not work out.
Why didnt it work out?
Her only son, John of Asturias, died shortly after his marriage.
Her daughter Isabella of Aragon, whose son Miguel da Paz died at the age of two, died in childbirth.

Question: Who ended up taking over?
Self-contained rewrite: Who ended up taking over for Isabella I of Castile?