RFamide Peptides in Early Vertebrate Development

Abstract

RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play.

Keywords: 26RFa/QRFP; GnIH; Kiss; NPFF; PrRP; RFa; brain development; early development.

Figure 1

Kiss and kiss receptors are expressed at very early stages in medaka embryos. Relative gene expression of kiss1 (A), kiss2 (B), gpr54-1 (C), and gpr54-2 (D) was analyzed at different developmental stages (mean ± SEM; n = 7). Key developmental stages are given above the age of the hours (h) or days (d) post-fertilization (hpf). The gene expression levels are given relative to a reference gene (β-actin). Different letters indicate significant differences (P < 0.05). Figure from Ref. (109).

Figure 2

Low dose antisense knockdown (KD) lead to impaired brain and eye development. kiss1 knockdown embryos showed impaired eye development at 1 dpf (top right). At 3 dpf, there was no development of the forebrain after kiss1 knockdown (bottom right). Scale bars correspond to 50 μm (top images) or 100 μm (bottom images). Arrowheads point to the area of the developing eyes. Figure from Ref. (109).