Mice Mutant in the DM Domain Gene Dmrt4 Are Viable and Fertile but Have Polyovular Follicles

ABSTRACT Proteins containing the DM domain, a zinc finger-like DNA binding motif, have been implicated in sexual differentiation in diverse metazoan organisms. Of seven mammalian DM domain genes, only Dmrt1 and Dmrt2 have been functionally analyzed. Here, we report expression analysis and targeted disruption of Dmrt4 (also called DmrtA1) in the mouse. Dmrt4 is widely expressed during embryonic and postnatal development. However, we find that mice homozygous for a putative null mutation in Dmrt4 develop essentially normally, undergo full sexual differentiation in both sexes, and are fertile. We observed two potential mutant phenotypes in Dmrt4 mutant mice. First, ovaries of most mutant females have polyovular follicles, suggesting a role in folliculogenesis. Second, 25% of mutant males consistently exhibited copulatory behavior toward other males. We also tested potential redundancy between Dmrt4 and two other gonadally expressed DM domain genes, Dmrt1 and Dmrt7. We observed no enhancement of gonadal phenotypes in the double mutants, suggesting that these genes function independently in gonadal development.

Download Full-text

Faculty Opinions recommendation of A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1088296.541320 ◽

2007 ◽

Author(s):

William Rainey

Keyword(s):

Nuclear Receptor ◽

Sexual Differentiation ◽

Gonadal Development ◽

A Cell

Download Full-text

Postnatal development of transmitter systems: Sexual differentiation of the gabaergic system and effects of muscimol

International Journal of Developmental Neuroscience ◽

10.1016/0736-5748(86)90049-3 ◽

1986 ◽

Vol 4 (4) ◽

pp. 319-326 ◽

Cited By ~ 22

Author(s):

G. Flügge ◽

W. Wuttke ◽

E. Fuchs

Keyword(s):

Postnatal Development ◽

Sexual Differentiation ◽

Gabaergic System

Download Full-text

Zinc-finger protein MdBBX7/MdCOL9, a target of MdMIEL1 E3 ligase, confers drought tolerance in apple

Plant Physiology ◽

10.1093/plphys/kiab420 ◽

2021 ◽

Author(s):

Pengxiang Chen ◽

Fang Zhi ◽

Xuewei Li ◽

Wenyun Shen ◽

Mingjia Yan ◽

...

Keyword(s):

Drought Stress ◽

Drought Tolerance ◽

Zinc Finger ◽

Zinc Finger Protein ◽

E3 Ligase ◽

26S Proteasome ◽

Negative Regulator ◽

Binding Motif ◽

Ethylene Response Factor ◽

Finger Protein

Abstract Water deficit is one of the main challenges for apple (Malus × domestica) growth and productivity. Breeding drought-tolerant cultivars depends on a thorough understanding of the drought responses of apple trees. Here, we identified the zinc-finger protein B-BOX 7/CONSTANS-LIKE 9 (MdBBX7/MdCOL9), which plays a positive role in apple drought tolerance. The overexpression of MdBBX7 enhanced drought tolerance, whereas knocking down MdBBX7 expression reduced it. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis identified one cis-element of MdBBX7, CCTTG, as well as its known binding motif, the T/G box. ChIP-seq and RNA-seq identified 1,197 direct targets of MdBBX7, including ETHYLENE RESPONSE FACTOR (ERF1), EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15), and GOLDEN2-LIKE 1 (GLK1) and these were further verified by ChIP-qPCR and electronic mobility shift assays. Yeast two-hybrid screen identified an interacting protein of MdBBX7, RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1). Further examination revealed that MdMIEL1 could mediate the ubiquitination and degradation of MdBBX7 by the 26S proteasome pathway. Genetic interaction analysis suggested that MdMIEL1 acts as an upstream factor of MdBBX7. In addition, MdMIEL1 was a negative regulator of the apple drought stress response. Taken together, our results illustrate the molecular mechanisms by which the MdMIEL1–MdBBX7 module influences the response of apple to drought stress.

Download Full-text

Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis, by Daniel D. Federman, M.D. Philadelphia and London: W. B. Saunders Co., 1967, 206 pp., $8.75

PEDIATRICS ◽

10.1542/peds.43.2.314a ◽

1969 ◽

Vol 43 (2) ◽

pp. 314-315

Author(s):

Alfred M. Bongiovanni

Keyword(s):

Differential Diagnosis ◽

Sexual Development ◽

Sexual Differentiation ◽

Gonadal Development ◽

Medical Texts ◽

General Physicians ◽

Precocious Development

There is much duplication in the area of medical texts, and so-called monographs often yield little that is not to be found in standard textbooks. Not so with Dr. Federman, who brings a special and personal flavor to his subject. He states that his monograph is "written for general physicians" and indeed the presentation is marked by clarity and breadth. He begins with a succinct description of normal sexual differentiation, proceeding to cytogenetics, disorders of gonadal development (appropriately subdivided), disorders of fetal endocrinology, and disorders of puberty, including delayed and precocious development.

Download Full-text

In Vivo Ablation of the Conserved GATA-Binding Motif in the Amh Promoter Impairs Amh Expression in the Male Mouse

Endocrinology ◽

10.1210/en.2019-00047 ◽

2019 ◽

Vol 160 (4) ◽

pp. 817-826 ◽

Cited By ~ 6

Author(s):

Marie France Bouchard ◽

Francis Bergeron ◽

Jasmine Grenier Delaney ◽

Louis-Mathieu Harvey ◽

Robert S Viger

Keyword(s):

Developmental Time ◽

Gonadal Development ◽

Conclusive Evidence ◽

Binding Motif ◽

Male Embryo ◽

Steroidogenic Factor 1 ◽

Protein Levels ◽

Positive Modulator ◽

And Function

Abstract GATA4 is an essential transcriptional regulator required for gonadal development, differentiation, and function. In the developing testis, proposed GATA4-regulated genes include steroidogenic factor 1 (Nr5a1), SRY-related HMG box 9 (Sox9), and anti-Müllerian hormone (Amh). Although some of these genes have been validated as genuine GATA4 targets, it remains unclear whether GATA4 is a direct regulator of endogenous Amh transcription. We used a CRISPR/Cas9-based approach to specifically inactivate or delete the sole GATA-binding motif of the proximal mouse Amh promoter. AMH mRNA and protein levels were assessed at developmental time points corresponding to elevated AMH levels: fetal and neonate testes in males and adult ovaries in females. In males, loss of GATA binding to the Amh promoter significantly reduced Amh expression. Although the loss of GATA binding did not block the initiation of Amh transcription, AMH mRNA and protein levels failed to upregulate in the developing fetal and neonate testis. Interestingly, adult male mice presented no anatomical anomalies and had no evidence of retained Müllerian duct structures, suggesting that AMH levels, although markedly reduced, were sufficient to masculinize the male embryo. In contrast to males, GATA binding to the Amh promoter was dispensable for Amh expression in the adult ovary. These results provide conclusive evidence that in males, GATA4 is a positive modulator of Amh expression that works in concert with other key transcription factors to ensure that the Amh gene is sufficiently expressed in a correct spatiotemporal manner during fetal and prepubertal testis development.

Download Full-text

Pod1 is involved in the sexual differentiation and gonadal development of the Nile tilapia

Science China Life Sciences ◽

10.1007/s11427-011-4240-4 ◽

2011 ◽

Vol 54 (11) ◽

pp. 1005-1010 ◽

Cited By ~ 2

Author(s):

JianZhong Li ◽

ShaoJun Liu ◽

Yoshitaka Nagahama

Keyword(s):

Sexual Differentiation ◽

Nile Tilapia ◽

Gonadal Development

Download Full-text

70 GONADAL DEVELOPMENT IN GUINEA PIG MALES (CAVIA PORCELLUS)

Reproduction Fertility and Development ◽

10.1071/rdv28n2ab70 ◽

2016 ◽

Vol 28 (2) ◽

pp. 164

Author(s):

F. Oliveira ◽

A. Santos ◽

A. A. Neto

Keyword(s):

Guinea Pig ◽

Sertoli Cells ◽

Sexual Differentiation ◽

Primordial Germ Cells ◽

Gonadal Development ◽

Postnatal Period ◽

Seminiferous Tubules ◽

Morphological Description ◽

Hormonal Function ◽

Gonad Differentiation

Sexual differentiation in mammals is an event that presents many variations between species. Because it is related to hormonal function, any imbalance in the androgens and estrogens production can lead to malformations. Because sexual differentiation occurs in different ways among various animals, the recognition of their peculiarities becomes important in order to correct reproductive handling in different species. Considering that the guinea pig is commonly used as an experimental model in the reproductive area, the goal of this work was to perform a morphological description of gonad differentiation of the male guinea pig during embryonic development. In total, 11 conceptuses with ages 25 (n = 3), 30 (n = 2), 40 (n = 2), 50 (n = 2), and 65 (n = 2) days were used for light microscopy processing. The embryos at 25 days were processed completely. For the others, the gonads were dissected. The samples were dehydrated in alcohol, embedded in paraffin, and 5-µm sections were stained with hematoxylin-eosin. In the guinea pig gonad at 25 days gestation, there was a presence of gonadal cords, formed by condensation of somatic cells, which is characteristic of an undifferentiated gonad. In addition, we observed the presence of mesonephric and paramesonephric ducts in different embryos, indicating that other genital system organs were not formed. For the 30 days of development of guinea pigs, we observed that gonadal cords were differentiated in testicular cords by invasion of mesenchymal and endothelial cells, and also composed of Sertoli cells and primordial germ cells. These cords were among a large amount of testicular mesenchyme at the 40-day group. With 50- and 65-day development samples, the gonad was completely differentiated into testicle, with the presence of spermatogonia and Sertoli cells in the seminiferous tubules, and a large amount of interstitial Leydig cells around the tubules. We conclude that gonadal differentiation in guinea pig males occurs around the middle of pregnancy, between 25 and 30 days and that, before the end of the pregnancy, at 50 days, the testicle presents morphology similar to that found in the postnatal period.

Download Full-text