In v4.2 we added support to define defaults in the designer, so starting with 4.2 you can define the default for the fields you want to have NEWSEQUENTIALID support for.
The default has to be defined on the field in the DB anyway, so even if it's defined at the designer level, the change has to be made in the DB as well. In v4.2 added defaults will result in an UPDATE DDL SQL script so the change will end up in the db that way.
When inserting a row, the field which has NEWSEQUENTIALID() as default will insert the value returned by the function call as the value for that field. A specific query is run right after the insert to obtain the inserted value (batched to the insert statement), and return it to engine to be inserted in the entity pk field. It only works for PK fields, and the field has to be null when inserted (so it's enough not to set it to a value).