Spatiotemporal cell expression of luteinizing hormone-releasing hormone in the prenatal mouse: evidence for an embryonic origin in the olfactory placode

Abstract

The spatiotemporal cell expression of luteinizing hormone-releasing hormone (LHRH) was investigated in mice during prenatal development using light microscopic immunocytochemistry. LHRH immunoreactive cells were first detected in the epithelium of the olfactory pit on gestational day $\text{11}\text{1}\text{2}$ (E11.5). Some LHRH cells were just outside the olfactory epithelium (OE), clustered on short ‘tracks’ which extended dorsocaudally. Immunopositive LHRH cells were not observed in any other regions. At E12.5, immunopositive cells were still detected in the OE, but now many LHRH cells were clustered on ‘tracks’ within olfactory areas. These ‘tracks’ started at the OE, bilaterally, and extended towards and abutted the basal telencephalic hemispheres. Some immunopositive cells were detected in the rostral telencephalon but not caudal to the telencephalon. The LHRH cells outside the OE were unipolar or bipolar, morphologically resembled mature LHRH neurons and appeared to contact neighboring LHRH cells. The distribution of LHRH cells at E13.5 was similar to E12.5, with the exception that immunopositive cells now extended from the telencephalon to the rostral diencephalon. From E14.5 to E17.5 the majority of LHRH cells were located within the forebrain; extending throughout the diencephalon. Immunopositive cells were not detected in the OE, but were scattered rostrocaudally in olfactory septal areas. By E16.5, LHRH cells within the brain were distributed in a pattern similar to that of the adult mouse. These findings illustrate that LHRH cells express their peptide phenotype early in ontogeny and before their distribution in the forebrain is detected. These data are consistent with the hypothesis that LHRH cells are derived from the olfactory placode and migrate into the forebrain during prenatal development.