René St-Arnaud¹, G. Antonio Candeliere¹, and Shoukat Dedhar²

¹Genetics Unit, Shriners Hospital, and Departments of Surgery and Human Genetics, McGill University, Montréal (Québec) Canada H3G1A6

²Division of Cancer Research and Department of Medical Biophysics, University of Toronto, Reichmann Research Building, Sunnybrook Health Science Centre, Toronto (Ontario) Canada M4N 3M5

Received 07/05/96; Accepted 07/12/96; On-line 08/01/96

Research on the vitamin D endocrine system is at a crossroad. Non-genomic responses to 1,25 (OH)₂D₃ have been described (reviewed in ref. 86) and mutant mice strains deficient in key vitamin D metabolic pathways have been engineered and begin to reveal new aspects of vitamin D function that were previously unrecognized (87). Concerning the vitamin D-dependent transcriptional responses, new VDRE structures have been characterized and novel VDR dimerization partners identified. Sequence similarity searches based on the non-classical response elements may identify previously unrecognized vitamin D-responsive genes. The characterization of additional factors interacting with the VDR, such as the osteoblast-specific NF-1 family member or transcriptional coactivators, is bound to reveal new information on the molecular mechanism of action of vitamin D. Finally, the interactions of the VDR with the multifunctional level have to be tested at the physiological level in vivo. The targeted inactivation of calreticulin in embryonic stem cells and the subsequently derived calreticulin 'knock-out' mice, already being studied in our laboratory, will unravel the role of calreticulin in embryonic development and vitamin D-mediated signal transduction.