Sex determination in Zebrafish ====================================== :Author: Hailing Fang :Created: June 11, 2024 :Updated: June 19, 2024 :Status: Draft; Errors This article briefly introduces sex determination in some vertebrates and then details the research progress on zebrafish sex determination. Primary Sex Determination and Secondary Sex Determination ---------------------------------------------------------------------------- The sex determination process can be divided into two stages in vertebrates: Primary Sex Determination and Secondary Sex Determination. In the first stage, the direction of gonadal development is determined, leading to differentiation into ovaries or testes. In the second stage, changes occur in the body's phenotype, the differentated gonad will generate sex homorns, and leading to the formation of sex-specific characteristics and functions. [1]_ Even thought those two stage of sex determination is well accepted, exspecially in mammal, the primary sex determination and second sex determination may not true for the birds [9]_. Sex Determination Mechanism in Vertebrates ----------------------------------------------------------------------------- This section describes sex determination in some clades (mammals, birds, reptiles, amphibians, and fish) of vertebrates. Since sex determination varies across these clades, establishing a universal pattern for any clade is currently not possible. The given sex determination patterns are specific to a limited number of species within each subdivision. Sex Determination in Mammals ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The sex of mammals is determined by sex chromosomes, XX for female, XY for male. No matter how many X chromosome an individual has, it will develop as male. [1]_ The sex-determining region on Y (SRY) play an important role in sex determination in mammals. [2]_ However, there are exception from the XY sex determination mechanism. *Myopus Schisticolor* is describes with fertile XY female. The The Y chromosome of these females is identical to that of males, and it is actually the X that causes sex-reversal: they carry a special variant of the X (called X*) which suppresses the male-determining function of the Y. [3]_ [4]_ *Ellobius lutescens* has lost Y chromosome, and with 17, X, and new sex determination mechanism alter out for this species [5]_ Sex Determination of Birds ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The sex determination of birds is determined by sex chromosomes. The embryo with two Z chromosomes (ZZ) develops into a male; the embryo with Z and W chromosomes (ZW) becomes female. [6]_ Chicken is most widly used aninimal model as a reprent of birds. It has 78 chromosomes, 10 pairs of macrochromosomes (Chromosomes 1–9, Z, and W) and 29 pairs of microchromosomes. The Z chromosome is far large than the W chromosome, 82 million bases versus 5.16 million bases. The male has two testes, and female has only ovary on the left [7]_. Two hypotheses exists on the sex determination of birds, one is called 'Z dosage' model, the other is called 'W dominant' model. In 'Z dosage model', a Z-linked gene is hypothesed, and tow copy of the gene is required for an individual develops into male, with observations that birds do not have dosage compensation system for the Z chromosome. The 'W dominant' proposed that a W linked genes will dorminate the birds develop into female, like SRY in Y chromosome to the male in mammals. Most evidence favours a Z chromosome dosage mechanism underling chicken sex determination, with little evidence of a role for the W chromosome. [8]_ Promising evidence indicates that the sex determination of birds may associated with cell autonomous sex identity (CASI). Naturelly, the gynandromorph chickens can occur rarely. The chicken has one side of the animal appears male and the other female duing to ZZ (male) and ZW (female) somatic cells. The gynandromorph chicken act as a proof for that the sexual phenotype are largely cell autonomous and not principally dependent on sex hormones. transplanting female pre-gonadal mesodermal tissue into male hosts and vice versa, prior to the time of gonadal sex differentiation, based on the expression of markers, the transplanted tissue differentiated into the sex of the donor, not the host. [9]_ Sex Determination in Reptiles ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The sex determination mechanism varies across different species within the clade. In snakes and lizards, sex is determined by inherited sex chromosomes, whereas in most turtles, sex is determined by the temperature at which the eggs are incubated. [10]_ Sex Determination in Amphibians ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Two chromosome sex determination systems, XY and ZW, exists in amphibians [11]_. And those two systems even can exists in same specie (frog Rana rugosa) [12]_ . Sex Determination in Fish ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Y. Kobayashi et al. [13]_ : .. Fishes exhibit a remarkable variety of sexuality. In many gonochoristic fishes, sex determination is genetic, i.e. males and females have different alleles or even different genes that specify their sexual morphology. In other cases, sex is determined by environmental variables such as temperature, pH, social condition, and salinity. Alternatively, many teleosts exhibit natural hermaphroditism where an individual changes from one sex to the other during adulthood. This unique feature of sexuality is limited only to fishes among the vertebrates. Some teleosts have gonads containing both mature ovaries and testes. In sequential hermaphroditism, some fishes change sex from male to female (protandrous sex change), others change from female to male (protogynous sex change), and a few change sex in both directions multiple times (bi-directional sex change). In many cases of sequential hermaphroditism, sex change is controlled by social cues such as the disappearance of a male or female from a group. Thus, the mechanisms of sex determination and differentiation in fishes are highly diverse and plastic, differing from those of other higher vertebrates. Here is an example that fish alter its sex. Clownfish are protandrous, meaning they start their lives as males and can change to females. They live in social hierarchies where the dominant fish is the female, and the next in line is a breeding male. The rest are smaller, non-breeding males. If the dominant female dies, the largest breeding male changes sex to become the new dominant female. The largest of the non-breeding males then becomes the new breeding male. [14]_ Sex Determination of Zebrafish -------------------------------------------------------------- Introduction ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The mechanisms of sex determination in domesticated zebrafish is not disclosed. The genetic and environmental factors can influence the sex of zebrafish. The sex of adult fish would not reversed in natural condition. [15]_ [16]_ Facts ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1. **Zebrafish in the wild have been found having sex determination, while Domesticated zebrafish do not** The zebrafish in the lab (demestic zebrafish) is devided from pet store, and the sex related chromosome can distingushed. While the zebrafish in wild can be determined using a ZW like genetic system (a regin in chromosome 4). 2. **The sex ratio depend on the parent fish** The sex ratio has a parents pair depended manual [17]_ 3. **adequate germ cells are required for female development** [18]_ 4. **Change sex ratio to bias male** Cyp19a1a mutants develop exclusively as fertile males. [15]_ 5. **Change sex ratio to bias female** Dmrt1 mutation [19]_ and 5-azacytidine treatment [20]_ would let the sex ratio female biased. References -------------------------------------------------------------------- .. [1] Gilbert, S. F. Chromosomal Sex Determination in Mammals. in Developmental Biology. 6th edition (Sinauer Associates, 2000) .. [2] Miyawaki, S. et al. The mouse Sry locus harbors a cryptic exon that is essential for male sex determination. Science 370, 121–124 (2020). .. [3] Gilbert, S. F. Chromosomal Sex Determination in Mammals. in Developmental Biology. 6th edition (Sinauer Associates, 2000). .. [4] Saunders, P. A. & Veyrunes, F. Unusual Mammalian Sex Determination Systems: A Cabinet of Curiosities. Genes (Basel) 12, 1770 (2021). .. [5] Mulugeta, E. et al. Genomes of Ellobius species provide insight into the evolutionary dynamics of mammalian sex chromosomes. Genome Res 26, 1202–1210 (2016). .. [6] Kuroiwa, A. Sex-Determining Mechanism in Avians. Adv Exp Med Biol 1001, 19–31 (2017). .. [7] Zhang, X., Li, J., Chen, S., Yang, N. & Zheng, J. Overview of Avian Sex Reversal. Int J Mol Sci 24, 8284 (2023). .. [8] Hirst, C. E., Major, A. T. & Smith, C. A. Sex determination and gonadal sex differentiation in the chicken model. The International Journal of Developmental Biology 62, 153–166 (2018). .. [9] Zhao, D. et al. Somatic sex identity is cell autonomous in the chicken. Nature 464, 237–242 (2010). .. [10] Gilbert, S. F. Environmental Sex Determination. in Developmental Biology. 6th edition (Sinauer Associates, 2000). .. [11] Nakamura, M. Sex determination in amphibians. Seminars in Cell & Developmental Biology 20, 271–282 (2009). .. [12] Nishioka M, Hanada H. Sex of reciprocal hybrids between the Hamakita (XX–XY type) population and the Murakami (ZW–ZZ type) population of Rana rugosa. Sci Rep Lab Amphib Biol Hiroshima Univ 1994;13:35–50. .. [13] Kobayashi, Y., Nagahama, Y. & Nakamura, M. Diversity and Plasticity of Sex Determination and Differentiation in Fishes. Sexual Development 7, 115–125 (2012). .. [14] https://en.wikipedia.org/wiki/Clownfish .. [15] Aharon, D. & Marlow, F. L. Sexual determination in zebrafish. Cell. Mol. Life Sci. 79, 8 (2021). .. [16] Kossack, M. E. & Draper, B. W. Genetic regulation of sex determination and maintenance in zebrafish (Danio rerio). Curr Top Dev Biol 134, 119–149 (2019). .. [17] Liew, W. C. et al. Polygenic Sex Determination System in Zebrafish. PLOS ONE 7, e34397 (2012). .. [18] Ye, D. et al. Abundance of Early Embryonic Primordial Germ Cells Promotes Zebrafish Female Differentiation as Revealed by Lifetime Labeling of Germline. Mar Biotechnol (NY) 21, 217–228 (2019). .. [19] Webster, K. A. et al. Dmrt1 is necessary for male sexual development in zebrafish. Developmental Biology 422, 33–46 (2017). .. [20] Ribas, L., Vanezis, K., Imués, M. A. & Piferrer, F. Treatment with a DNA methyltransferase inhibitor feminizes zebrafish and induces long-term expression changes in the gonads. Epigenetics & Chromatin 10, 59 (2017).