Abstract
In mammals the melanocortin 4 receptor (Mc4r) signaling system has been mainly associated with the regulation of appetite and energy homeostasis. In fish of the genus Xiphophorus (platyfish and swordtails) puberty onset is genetically determined by a single locus, which encodes the mc4r. Wild populations of Xiphophorus are polymorphic for early and late-maturing individuals. Copy number variation of different mc4r alleles is responsible for the difference in puberty onset. To answer whether this is a special adaptation of the Mc4r signaling system in the lineage of Xiphophorus or a more widely conserved mechanism in teleosts, we studied the role of Mc4r in reproductive biology of medaka (Oryzias latipes), a close relative to Xiphophorus and a well-established model to study gonadal development. To understand the potential role of Mc4r in medaka, we characterized the major features of the Mc4r signaling system (mc4r, mrap2, pomc, agrp1). In medaka, all these genes are expressed before hatching. In adults, they are mainly expressed in the brain. The transcript of the receptor accessory protein mrap2 co-localizes with mc4r in the hypothalamus in adult brains indicating a conserved function of modulating Mc4r signaling. Comparing growth and puberty between wild-type and mc4r knockout medaka revealed that absence of Mc4r does not change puberty timing but significantly delays hatching. Embryonic development of knockout animals is retarded compared to wild-types. In conclusion, the Mc4r system in medaka is involved in regulation of growth rather than puberty.
Highlights
Puberty is the process through which an individual develops from an immature to the mature stage and obtains first time the capability to reproduce
Through analysis of the temporal and spatial expression profile and functional studies on mc4r mutants, we find that the role of mc4r is related to development and growth in medaka, like in zebrafish, but not to controlling puberty timing like in Xiphophorus fish
As the first step toward an investigation of the melanocortin 4 receptor (Mc4r) signaling system genes in medaka fish, we performed an evolutionary analysis of Mc4r signaling system genes in various fish
Summary
Puberty is the process through which an individual develops from an immature to the mature stage and obtains first time the capability to reproduce. This process can be affected by both the genetic background and environmental factors [1, 2]. Teleost fish of the genus Xiphophorus (platyfish and swordtails) show polymorphisms in puberty onset timing, body length and reproduction tactics [3]. The P (Puberty) locus encoding the melanocortin 4 receptor (Mc4r) is critically involved in establishing these polymorphisms [4, 5]. Distinct alleles of mc4r and copy number variation of these alleles determine the onset of puberty to be early or late [4].
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