Development of the mouse suprachiasmatic nucleus: Determination of time of cell origin and spatial arrangements within the nucleus

The suprachiasmatic nucleus (SCN) in mammals functions as the principal circadian pacemaker synchronizing diverse physiological and behavioral processes to environmental stimuli. It consists of heterogeneous populations of cells with unique spatial organization that can vary among species, but are commonly discussed within a framework of two principal regions, the ventrolateral or dorsomedial halves of the nucleus or in other instances the core and shell. In both hamsters and rats, cells of different SCN regions have been shown to have different developmental histories. Using bromodeoxyuridine as a marker of cell division, the present study investigated the time of SCN cell origin in mice (C57BL/6) and their settling patterns within the nucleus. Results show that SCN cytogenesis occurs between embryonic days 12 and 15 and is complete 5 days prior to birth. Cells born on embryonic day 12 are mainly confined to a ventrolateral region of the mid-SCN, whereas cells produced later on embryonic days 13.5 and 14.5 form a cap around the cells produced first and extend into the posterior and anterior ends of the nucleus. These results suggest an ordered spatiotemporal program of SCN cytogenesis whereby a mid-SCN core is born first followed by a surrounding shell of later-born cells. Variations in cytogenesis could affect the relative sizes of different SCN regions and, thereby, affect its function. The relative contributions of a highly ordered program of cytogenesis and intercellular interactions after postmitotic cells leave the germinal epithelium remain to be determined.