Role of autonomous and non-autonomous sex determination signals in sexually dimorphic development of the Drosophila embryonic gonad

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.

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Long-Range Regulation of Key Sex Determination Genes

Sexual Development ◽

10.1159/000519891 ◽

2021 ◽

pp. 1-21

Author(s):

Roberta Migale ◽

Michelle Neumann ◽

Robin Lovell-Badge

Keyword(s):

Sex Determination ◽

Long Range ◽

Current Knowledge ◽

Disorders Of Sex Development ◽

Sexually Dimorphic ◽

Protein Coding ◽

Sex Development ◽

Human Disorders ◽

The Many

The development of sexually dimorphic gonads is a unique process that starts with the specification of the bipotential genital ridges and culminates with the development of fully differentiated ovaries and testes in females and males, respectively. Research on sex determination has been mostly focused on the identification of sex determination genes, the majority of which encode for proteins and specifically transcription factors such as SOX9 in the testes and FOXL2 in the ovaries. Our understanding of which factors may be critical for sex determination have benefited from the study of human disorders of sex development (DSD) and animal models, such as the mouse and the goat, as these often replicate the same phenotypes observed in humans when mutations or chromosomic rearrangements arise in protein-coding genes. Despite the advances made so far in explaining the role of key factors such as SRY, SOX9, and FOXL2 and the genes they control, what may regulate these factors upstream is not entirely understood, often resulting in the inability to correctly diagnose DSD patients. The role of non-coding DNA, which represents 98% of the human genome, in sex determination has only recently begun to be fully appreciated. In this review, we summarize the current knowledge on the long-range regulation of 2 important sex determination genes, <i>SOX9</i> and <i>FOXL2</i>, and discuss the challenges that lie ahead and the many avenues of research yet to be explored in the sex determination field.

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The Role of Sonic Hedgehog-Gli2 Pathway in the Masculinization of External Genitalia

Endocrinology ◽

10.1210/en.2011-0263 ◽

2011 ◽

Vol 152 (7) ◽

pp. 2894-2903 ◽

Cited By ~ 42

Author(s):

Shinichi Miyagawa ◽

Daisuke Matsumaru ◽

Aki Murashima ◽

Akiko Omori ◽

Yoshihiko Satoh ◽

...

Keyword(s):

Signaling Pathway ◽

Sonic Hedgehog ◽

Hedgehog Signaling ◽

External Genitalia ◽

Sexually Dimorphic ◽

Hedgehog Signaling Pathway ◽

Initial Development ◽

Urethral Plate ◽

Male External Genitalia

During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.

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The role of genetic mechanisms of sex determination in the survival of small populations of Silene littorea: A reintroduction experiment

Biological Conservation ◽

10.1016/j.biocon.2005.10.028 ◽

2006 ◽

Vol 129 (1) ◽

pp. 124-133 ◽

Cited By ~ 4

Author(s):

Carlos Vilas ◽

Carlos García

Keyword(s):

Sex Determination ◽

Small Populations ◽

Genetic Mechanisms

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Carotenoid-based plumage colouration in red bishops (Euplectes orix) — signalling presence rather than quality?

Behaviour ◽

10.1163/000579511x608693 ◽

2011 ◽

Vol 148 (11-13) ◽

pp. 1372-1392 ◽

Cited By ~ 3

Author(s):

Alice U. Edler ◽

Thomas W.P. Friedl

Keyword(s):

Reproductive Success ◽

Parasite Load ◽

Blood Parasite ◽

Male Reproductive Success ◽

Sexually Dimorphic ◽

Male Quality ◽

Plumage Colouration ◽

Selection For ◽

Breeding Plumage

AbstractThe role of bright plumage colouration for female choice has been the focus of research in sexual selection for many years, with several studies showing that females prefer the most elaborately ornamented males, which are often also the highest quality individuals. Here, we analysed the associations between reproductive performance and plumage, body condition and blood parasite load in the red bishop (Euplectes orix), a sexually dimorphic and polygynous weaverbird species, where males in a carotenoid-based orange-to-red breeding plumage defend territories and build many nests to which they try to attract females. Male reproductive success in terms of number of nests accepted was mainly determined by the number of nests built, but was also positively related to blood parasite load, while we found no influence of plumage characteristics. Together with previously obtained data, our results indicate that plumage characteristics in the red bishop do not affect male reproductive success and are generally not suitable to reliably indicate male quality. We suggest that the primary function of the brilliant orange-scarlet breeding plumage might be presence signalling in terms of increasing conspicuousness of breeding males to females searching for mates.

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The dual role of hermaphrodite in the Drosophila sex determination regulatory hierarchy

Development ◽

10.1242/dev.121.1.99 ◽

1995 ◽

Vol 121 (1) ◽

pp. 99-111 ◽

Cited By ~ 6

Author(s):

M.A. Pultz ◽

B.S. Baker

Keyword(s):

Sex Determination ◽

Dosage Compensation ◽

Regulatory Protein ◽

Female Offspring ◽

Normal Female ◽

Female Development ◽

Salivary Gland Cells ◽

Maternal Function ◽

Different Levels

The hermaphrodite (her) locus has both maternal and zygotic functions required for normal female development in Drosophila. Maternal her function is needed for the viability of female offspring, while zygotic her function is needed for female sexual differentiation. Here we focus on understanding how her fits into the sex determination regulatory hierarchy. Maternal her function is needed early in the hierarchy: genetic interactions of her with the sisterless genes (sis-a and sis-b), with function-specific Sex-lethal (Sxl) alleles and with the constitutive allele SxlM#1 suggest that maternal her function is needed for Sxl initiation. When mothers are defective for her function, their daughters fail to activate a reporter gene for the Sxl early promoter and are deficient in Sxl protein expression. Dosage compensation is misregulated in the moribund daughters: some salivary gland cells show binding of the maleless (mle) dosage compensation regulatory protein to the X chromosome, a binding pattern normally seen only in males. Thus maternal her function is needed early in the hierarchy as a positive regulator of Sxl, and the maternal effects of her on female viability probably reflect Sxl's role in regulating dosage compensation. In contrast to her's maternal function, her's zygotic function in sex determination acts at the end of the hierarchy. This zygotic effect is not rescued by constitutive Sxl expression, nor by constitutive transformer (tra) expression. Moreover, the expression of doublesex (dsx) transcripts appears normal in her mutant females. We conclude that the maternal and zygotic functions of her are needed at two distinctly different levels of the sex determination regulatory hierarchy.

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