Prenatal development of the retinohypothalamic pathway and the suprachiasmatic nucleus in the sheep

Circadian rhythms are present during fetal life in several mammalian species. To characterize the ontogeny of the neural mechanisms that account for circadian rhythmicity in a precocious species, we studied the prenatal development of the retinohypothalamic pathway in lambs (gestation period of 147 days), using horseradish peroxidase and wheat germ agglutinin as anterograde tracers. The suprachiasmatic nucleus was present as early as embryonic day 52 (E52). After E58, the suprachiasmatic nucleus reached its full number of neurons, estimated by the disector method in about 160,000 cells per nucleus at E62. The retinohypothalamic axons invaded the suprachiasmatic nucleus from E58, while neuroblasts were still migrating to the nucleus. At E62, there was a strong retinal projection that evolved until E121, when the retinal afferents established their definitive pattern of distribution in the ventral and central regions of the suprachiasmatic nucleus, and adjacent hypothalamic structures. The development of the retinohypothalamic pathway was delayed by about a week relative to the innervation of other subcortical visual centers. The present findings demonstrated an early prenatal development of the visual pathways in lambs, including the retinohypothalamic pathway, suggesting that the mechanisms for the visual entrainment of circadian rhythms in lambs may be functioning several weeks before birth.