Abstract
Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.
Highlights
Germ cells carry the task of reproduction and creating diversity for sexually reproducing species
To examine the potential functional requirement of Igsf11 during meiosis, we generated a meiotic reporter system which allows us to examine the progression of meiotic prophase I and isolate meiotic cells from mouse testis
When the expression of Igsf11 was compared between Sertoli cells and spermatogenic cells (Figs 2G, S3D and S4C), we found a low but detectable level of Igsf11 in Sertoli cells, which exhibited a slight upregulation after 25 dpp, and the expression level was always lower
Summary
Germ cells carry the task of reproduction and creating diversity for sexually reproducing species In mammals, both male and female germ cells undergo meiosis with the support of gonadal somatic cells, their surrounding microenvironments are quite different. Igsf, which belongs to the CTX family of immunoglobulin like cell adhesion molecule (IgCAMs, or immunoglobulin superfamily, IgSF), was identified in 2002 and found to be preferentially expressed in testis and brain [4]. This family of proteins are single-pass type I transmembrane glycoprotein and contain a membrane-distal V-type and a C2-type domain in their extracellular region [5]. It is not clear if IGSF11 is required in germ cells or for progression of meiosis
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