Dynamic patterned expression of orphan nuclear receptor genes RORalpha and RORbeta in developing mouse forebrain

Abstract

As a step toward using two closely related members of the nuclear receptor family, RORalpha and RORbeta, as markers and tools for genetic manipulations in mouse forebrain, we have used in situ hybridization to analyze their expression from E10.5 to P7. At later embryonic and early postnatal ages, RORalpha expression in dorsal thalamus is mainly limited to robust expression throughout the principal sensory nuclei. RORbeta is expressed in a similar set of dorsal thalamic nuclei as RORalpha, but exhibits a more limited expression within the principal sensory nuclei. RORalpha is expressed as early as E12.5 in dorsal thalamus by presumptive ventroposterior neurons, whereas RORbeta expression is not detected until later embryonic ages. RORbeta is highly expressed in embryonic neocortex, and exhibits strongly graded rostrocaudal and lateromedial patterns of expression. Over the first postnatal week, the graded expression of RORbeta gradually acquires a disjunctive pattern largely restricted to layers 4 and 5 of the primary sensory areas. In contrast, very weak RORalpha expression is first detected in the neocortex just around birth, and is limited to the middle layer of the cortical plate of the putative somatosensory area. Later, a limited and very weak RORalpha expression is evident mainly in layer 4 of more caudal areas. To determine whether patterned retinal input is required for the proper postnatal expression and patterning of RORalpha and RORbeta, we performed neonatal bilateral enucleations. We did not detect any significant differences between normal and enucleated mice in expression in visual areas. Although TCA input may be required for proper regulation of the postnatal expression of RORalpha and RORbeta, these findings suggest that aspects of the dynamic postnatal expression and patterning of these genes are regulated independently of patterned visual activity relayed by geniculocortical afferents. The patterned expression of RORalpha in dorsal thalamus suggests that this gene locus may be useful to genetically modify the development of dorsal thalamus and thalamocortical projections.