Dataset Information

Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse.

ABSTRACT: Primordial germ cells (PGCs) are a highly migratory cell population that gives rise to eggs and sperm. Much is known about PGC specification, but less about the processes that control PGC migration. In this study, we document a deficiency in PGC development in embryos carrying global homozygous null mutations in Msx1 and Msx2, both immediate downstream effectors of Bmp signaling pathway. We show that Msx1(-/-);Msx2(-/-) mutant embryos have defects in PGC migration as well as a reduced number of PGCs. These phenotypes are also evident in a Mesp1-Cre-mediated mesoderm-specific mutant line of Msx1 and Msx2. Since PGCs are not marked in Mesp1-lineage tracing, our results suggest that Msx1 and Msx2 function cell non-autonomously in directing PGC migration. Consistent with this hypothesis, we noted an upregulation of fibronectin, well known as a mediator of cell migration, in tissues through which PGCs migrate. We also noted a reduction in the expression of Wnt5a and an increase in the expression in Bmp4 in such tissues in Msx1(-/-);Msx2(-/-) mutants, both known effectors of PGC development.

SUBMITTER: Sun J

PROVIDER: S-EPMC5407493 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse.

Sun Jingjing J Ting Man-Chun MC Ishii Mamoru M Maxson Robert R

Developmental biology 20160718 1

Primordial germ cells (PGCs) are a highly migratory cell population that gives rise to eggs and sperm. Much is known about PGC specification, but less about the processes that control PGC migration. In this study, we document a deficiency in PGC development in embryos carrying global homozygous null mutations in Msx1 and Msx2, both immediate downstream effectors of Bmp signaling pathway. We show that Msx1(-/-);Msx2(-/-) mutant embryos have defects in PGC migration as well as a reduced number of ...[more]

PMID: 27435625

Similar Datasets

Project description:BackgroundMicroRNAs (miRNAs) are critical regulators of transcriptional and post-transcriptional gene silencing, which are involved in multiple developmental processes in many organisms. Apart from miRNAs, mouse germ cells express another type of small RNA, piwi-interacting RNAs (piRNAs). Although it has been clear that piRNAs play a role in repression of retrotransposons during spermatogenesis, the function of miRNA in mouse germ cells has been unclear.Methodology/principal findingsIn this study, we first revealed the expression pattern of miRNAs by using a real-time PCR-based 220-plex miRNA expression profiling method. During development of germ cells, miR-17-92 cluster, which is thought to promote cell cycling, and the ES cell-specific cluster encoding miR-290 to -295 (miR-290-295 cluster) were highly expressed in primordial germ cells (PGCs) and spermatogonia. A set of miRNAs was developmentally regulated. We next analysed function of miRNA biogenesis in germ cell development by using conditional Dicer-knockout mice in which Dicer gene was deleted specifically in the germ cells. Dicer-deleted PGCs and spermatogonia exhibited poor proliferation. Retrotransposon activity was unexpectedly suppressed in Dicer-deleted PGCs, but not affected in the spermatogonia. In Dicer-deleted testis, spermatogenesis was retarded at an early stage when proliferation and/or early differentiation. Additionally, we analysed spermatogenesis in conditional Argonaute2-deficient mice. In contrast to Dicer-deficient testis, spermatogenesis in Argonaute2-deficient testis was indistinguishable from that in wild type.Conclusion/significanceThese results illustrate that miRNAs are important for the proliferation of PGCs and spermatogonia, but dispensable for the repression of retrotransposons in developing germ cells. Consistently, miRNAs promoting cell cycling are highly expressed in PGCs and spermatogonia. Furthermore, based on normal spermatogenesis in Argonaute2-deficient testis, the critical function of Dicer in spermatogenesis is independent of Argonaute2.

Project description:BackgroundExploring the molecular mechanisms of primordial germ cell (PGC) migration and the involvement of gonadal somatic cells in gonad development is valuable for comprehending the origins and potential treatments of reproductive-related diseases.MethodsDiaphanous related formin 1 (Diaph1, also known as mDia1) was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). Subsequently, the CRISPR-Cas9 technology was used to construct Diaph1 knockout mice to investigate the role of Diaph1 in gonad development.ResultsBased on data from public databases, a differentially expressed gene Diaph1, was identified in the migration of mouse PGC. Additionally, the number of PGCs was significantly reduced in Diaph1 knockout mice compared to wild type mice, and the expression levels of genes related to proliferation (Dicer1, Mcm9), adhesion (E-cadherin, Cdh1), and migration (Cxcr4, Hmgcr, Dazl) were significantly decreased. Diaph1 knockout also inhibited Leydig cell proliferation and induced apoptosis in the testis, as well as granulosa cell apoptosis in the ovary. Moreover, the sperm count in the epididymal region and the count of ovarian follicles were significantly reduced in Diaph1 knockout mice, resulting in decreased fertility, concomitant with lowered levels of serum testosterone and estradiol. Further research found that in Diaph1 knockout mice, the key enzymes involved in testosterone synthesis (CYP11A1, 3β-HSD) were decreased in Leydig cells, and the estradiol-associated factor (FSH receptor, AMH) in granulosa cells were also downregulated.ConclusionsOverall, our findings indicate that the knockout of Diaph1 can disrupt the expression of factors that regulate sex hormone production, leading to impaired secretion of sex hormones, ultimately resulting in damage to reproductive function. These results provide a new perspective on the molecular mechanisms underlying PGC migration and gonadal development, and offer valuable insights for further research on the causes, diagnosis, and treatment of related diseases.

Dataset Information

Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse.

Publications

Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets