Abnormal development of the suprachiasmatic nuclei of the hypothalamus in a strain of genetically anophthalmic mice.

In the anophthalmic mutant of the mouse the optic primordia are "genetically enucleated" well before the usual emergence of retinal ganglion cell axons (Silver and Hughes, '74). In eyeless animals, a portion of the mediobasal hypothalamus and one of its constituent nuclear pairs, nucleus suprachiasmaticus (SCN), were markedly abnormal in the embryo and adult. It has been reported that the ventral portion of the SCN receives a substantial, direct retinal innervation (Moore and Lenn, '72) and that these nuclei may mediate several light-induced hormonal and behavioral circadian rhythms (Stetson and Whitmyre, '76). During day 13 of mutant embryogenesis, just prior to the time of optic chiasm formation in normal animals, a large portion of ependyma and adjacent brain tissue herniated into the lumen of the would-be suprachiasmatic region of the third ventricle. In 70% of the animals examined histologically during the latter phase of development and as adults, regulation occurred and the brains were largely comparable with those of controls. However, in the remaining mutant mice, the overall size of either, or sometimse both, SCN was much reduced. The basal (but not the apical) dendrites of SCN neurons failed to develop fully. Some basal dendrites normally invade the optic chiasm below. In several mutant animals one or the other SCN had greatly increased numbers of cells, while the contralateral one had diminished numbers. These observations suggest that regular formation of the suprachiasmatic region of the hypothalamus and especially the suprachiasmatic nuclei, may depend during development upon the presence of the eye or the subjacent optic axons.