Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†

Abstract

Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

“…Vascularization is crucial for the delivery of exogenous factors in the testicular compartments, in the initial organization of the testis cords, and also in the regulation of testis morphogenesis [4,7,10]. It is also required for maintaining the interstitial progenitor population of the fetal Leydig cells [10][11][12].…”

Uncovering the prominent role of satellite cells in paravertebral muscle development and aging by single-nucleus RNA sequencing

“…Then, we carried out biological annotations according to the literature and annotated eight cell types ( Fig. 1 B), SCs (expressing Myod1 , 32 Myog , 33 Cd82 , 34 Myl9 35 ), FMCs (expressing Myh1 36 and Myh2 37 ), SMCs (expressing Myh7 , 37 Myl2 , 38 Myl3 39 ), fibro/adipogenic progenitors (FAPs, expressing Dcn 40 and Pdgfra 32 ), fibroblasts (expressing Nrg1 41 and Erbb4 42 ), adipocytes (expressing Tfrc 43 and Dlk2 44 ), macrophages (expressing Maf 45 ), and ECs (expressing Pecam1 46 and Flt1 47 ) ( Fig. 1 B, C, G).…”

NR2F2 is required in the embryonic testis for Fetal Leydig Cell development

“…Paracrine signals acting on progenitors converge to regulate the transcription factors NR5A1, GATA4 and GATA6 which drive FLC differentiation by controlling the expression of genes related to cholesterol metabolism and steroidogenesis (33)(34)(35)(36)(37)(38)(39). In addition to the paracrine signals, interstitial steroidogenic progenitors differentiation along the FLC lineage is also regulated by the cell-autonomous action of the transcription factors ARX, TCF21, PBX1, MAF and MAFB, although their precise roles remain elusive (5,(40)(41)(42)(43).…”