Ontogeny of angiotensin II type 2 receptor mRNA expression in fetal and neonatal rat brain

Abstract

Recent studies have provided evidence for a specific role of the angiotensin II type 2 receptor (AT2) in in vitro neuron differentiation, and in AT2 knock-out mice that display central neurological anomalies. The role of AT2 in brain development is currently unknown. By using radiolabeled cRNA probes for in situ hybridization histochemistry, we determined the ontogenic development of AT2 mRNA in fetal and neonatal rat brain, from 11 days of gestation (E11) to 28 days postnatal (P28). Brain AT2 mRNA is first detected in the lateral hypothalamic neuroepithelium at E13. AT2 mRNA is detected beginning at E15 in the subthalamic and hypoglossus nuclei; at E17 in the pedunculopontine nucleus, cerebellum, motor facial nucleus, and the inferior olivary complex; at E19 in the thalamus, bed nucleus of the supraoptic decussation, interstitial nucleus of Cajal, nuclei of the lateral lemniscus, locus coeruleus, and supragenual nucleus; and at E21 in the lateral septal and medial amygdaloid nuclei, medial geniculate body, and the superior colliculus. The substantia nigra and many telencephalic and medullary nuclei express AT2 mRNA only after birth. Certain structures express AT2 mRNA strongly but transiently during embryonic life, such as the differentiating lateral hypothalamic area at E13, the superior olivary complex at E19 and E21, and the red nucleus at E15 and E17. In conclusion, during brain development, expression of AT2 mRNA appears early at E13, is strongly but transiently expressed in certain structures, and is high and persists until brain maturity in nuclei involved in motor functions and sensory integration. Our results support a dual role of AT2 during brain development in early maturation and differentiation, but also in modulation of established functions during perinatal and adult life.