Biology subjects

Yan, Y.-l.

Publications and source records attributed to Yan, Y.-l..

3 recordsLinked to original sources

bioRxiv2019

The roles of Amh in zebrafish gonad development and sex determination

Fetal mammalian testes secrete Amh (Anti-Mullerian hormone), which inhibits female reproductive tract (Mullerian duct) development. Amh also derives from mature mammalian ovarian follicles, which marks oocyte reserve and characterizes PCOS (polycystic ovarian syndrome). Zebrafish (Danio rerio) lacks Mullerian ducts and the Amh receptor gene amhr2 but, curiously, retains amh. To discover the roles of Amh in the absence of Mullerian ducts and the ancestral receptor gene, we made amh null alleles in zebrafish. Results showed that normal amh prevents female-biased sex ratios. Adult male amh mutants had enormous testes, half of which contained immature oocytes, demonstrating that Amh regulates male germ cell accumulation and inhibits oocyte development or survival. Mutant males formed sperm ducts and some produced a few offspring. Young female mutants laid a few fertile eggs, so they also had functional sex ducts. Older amh mutants accumulated non-vitellogenic follicles in exceedingly large but sterile ovaries, showing that Amh helps control ovarian follicle maturation and proliferation. RNA-seq data partitioned 21-day post-fertilization (dpf) juveniles into two groups that each contained mutant and wild type fish. Group21-1 up-regulated ovary genes compared to Group21-2, which were likely developing as males. By 35dpf, transcriptomes distinguished males from females and, within each sex, mutants from wild types. In adult mutants, ovaries greatly under-expressed granulosa and theca genes and testes under-expressed Leydig cell genes. These results show that ancestral Amh functions included development of the gonadal soma in ovaries and testes and regulation of gamete proliferation and maturation. A major gap in our understanding is the identity of the gene encoding a zebrafish Amh receptor; we show here that the loss of amhr2 is associated with the breakpoint of a chromosome rearrangement shared among cyprinid fishes.\n\nArticle SummaryAnti-Mullerian hormone (Amh) inhibits female reproductive duct development, signals oocyte reserve, and marks polycystic ovarian syndrome. Zebrafish lacks Mullerian ducts and the typical Amh receptor, questioning evolving roles of Amh. We made knockout mutations in zebrafish amh. Most mutants were female and the few males often had oocytes in their testes, showing that Amh promotes male development. Mutant reproductive ducts functioned, but testes were enormous and ovaries accumulated immature oocytes, showing that Amh regulates germ cell proliferation and maturation. Transcriptomics revealed that Amh controls development of steroid-producing gonad cells. Amh in zebrafish preserved ancestral roles despite losing Mullerian ducts and the Amh receptor.

genetics↗

bioRxiv2018

Developmental tuning of mineralization drives morphological diversity of gill cover bones in sculpins and their relatives

The role of osteoblast placement in skeletal morphological variation is relatively wellunderstood, but alternative developmental mechanisms affecting bone shape remain largely unknown. Specifically, very little attention has been paid to variation in later mineralization stages of intramembranous ossification as a driver of morphological diversity. We discover the occurrence of specific, sometimes large regions of nonmineralized osteoid within bones that also contain mineralized tissue. We show through a variety of histological, molecular, and tomographic tests that this \"extended\" osteoid material is most likely nonmineralized bone matrix. This tissue type is a significant determinant of gill cover bone shape in the teleostean suborder Cottoidei. We demonstrate repeated evolution of extended osteoid in Cottoidei through ancestral state reconstruction and test for an association between its presence and habitat differences among species. Through measurement of extended osteoid at various stages of gill cover development in species across the phylogeny, we gain insight into possible evolutionary developmental origins of the trait. We conclude that this finetuned developmental regulation of bone matrix mineralization reflects heterochrony at multiple biological levels and is a novel mechanism for the evolution of diversity in skeletal morphology. This research lays the groundwork for a new model in which to study bone mineralization and evolutionary developmental processes, particularly as they may relate to adaptation during a prominent evolutionary radiation of fishes.

evolutionary biology↗

bioRxiv2018

wnt4a Promotes Female Development and Reproductive Duct Elongation in Zebrafish

In laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as male or female. Many sex determination and differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Mullerian duct development, where it function, in part, to antagonize the male-promoting FGF9 signal. Wnt4 is highly conserved in non-mammalian vertebrates, but it is not known if Wnt4 plays a role in sex determination and/or the differentiation of sex organs outside of mammals. This is an especially interesting question in teleost, such as zebrafish, because they lack an Fgf9 ortholog. Here we show that wnt4a is the ortholog of mammalian Wnt4, and that wnt4b was present in the last common ancestor of humans and zebrafish, but was lost in mammals. We found that wnt4a is expressed in the somatic cells of juvenile gonads during the time sex determination likely occurs. We show that wnt4a loss-of-function mutants develop predominantly as males and conclude that wnt4a activity promotes female sex determination in zebrafish. Additionally, both male and female wnt4a mutants are sterile because their reproductive ducts do not connect to the vent, where wnt4a is normally expressed. Yet when dissected from homozygous wnt4a mutant gonads, both sperm and eggs can produce fertile offspring. Together these results strongly argue that Wnt4a is a conserved regulator of female sex determination and reproductive duct development in non-mammalian vertebrates.\n\nSUMMARYWnt4 is a key regulator of ovary development in mammals, but it is not known if it plays a similar role in other vertebrates. Here we show that zebrafish wnt4a is the ortholog of mammalian Wnt4. We show that wnt4a is expressed in zebrafish somatic gonad cells during the time sex determination likely occurs. Through analysis of wnt4a mutants, we show that Wnt4a promotes female sex determination and the development of the male and female reproductive. We conclude that Wnt4/Wnt4a is likely a conserved regulator of ovarian and reproductive duct development in all vertebrates

developmental biology↗