Biology subjects

DeFalco, T.

Publications and source records attributed to DeFalco, T..

5 recordsLinked to original sources

bioRxiv2021

Perivascular cells support folliculogenesis in the developing ovary

Granulosa cells, supporting cells of the ovary, are essential for ovarian differentiation by providing a nurturing environment for oogenesis. Sufficient numbers of granulosa cells are vital for establishment of follicles and the oocyte reserve; therefore, identifying the cellular source from which granulosa cells are derived is critical for understanding basic ovarian biology. One cell type that has received little attention in this field is the perivascular cell. Here we use lineage tracing and organ culture techniques in mice to identify ovarian Nestin+ perivascular cells as multipotent progenitors that contribute to granulosa, thecal, and pericyte lineages. Maintenance of these progenitors was dependent on vascular-mesenchymal Notch signaling. Ablation of postnatal Nestin+ cells resulted in a disruption of granulosa cell specification and an increased incidence of polyovular ovarian follicles, thus uncovering key roles for vasculature in ovarian differentiation. These findings may provide new insights into the origins of female gonad dysgenesis and infertility.

developmental biology↗

bioRxiv2021

Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis

Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture progressively maturing germ cells. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, are vital for successful spermatogenesis. However, the mechanisms and developmental timing that underlie the establishment of polarity are poorly understood. To investigate this aspect of testicular function, we conditionally deleted Cdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells. Cdc42 deletion disrupted adult Sertoli cell maturation and localization of polarity proteins, but did not affect fetal and early postnatal testicular development, nor the onset of the first wave of spermatogenesis. By early adulthood, however, conditional knockout males exhibited a loss of spermatogenic cells, resulting in a complete lack of sperm. These findings demonstrate that Cdc42 plays an essential role in establishing adult Sertoli cell polarity and, thus, maintaining steady-state spermatogenesis and healthy sperm production.

developmental biology↗

bioRxiv2021

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

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. Summary statementDeletion of Mafb and Maf genes leads to supernumerary monocytes in fetal mouse gonads, resulting in vascular, morphogenetic, and differentiation defects during testicular organogenesis.

developmental biology↗

bioRxiv2021

Polycomb suppresses a female gene regulatory network in Sertoli cells

Gonadal sex determination is controlled by the support cells of testes and ovaries. In testes, the epigenetic mechanism that maintains cellular memory to suppress female sexual differentiation remains unknown. Here, we show that Polycomb suppresses a female gene regulatory network in Sertoli cells, the specific support cells for postnatal testes. Through genetic ablation, we removed Polycomb repressive complex 1 (PRC1) from embryonic Sertoli cells after sex determination. PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed the specific, critical genes required for granulosa cells, the support cells of ovaries, thereby inactivating the female gene regulatory network. The underlying chromatin of female genes was coated with Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, we identify a critical mechanism centered on Polycomb that maintains the male fate in adult testes.

developmental biology↗

bioRxiv2020

FERONIA regulates FLS2 plasma membrane nanoscale dynamics to modulate plant immune signaling

Spatial partitioning is a propensity of biological systems orchestrating cell activities in space and time. The dynamic regulation of plasma membrane nano-environments has recently emerged as a key fundamental aspect of plant signaling, but the molecular components governing it are still mostly unclear. The receptor kinase FERONIA (FER) controls complex formation of the immune receptor kinase FLAGELLIN SENSING 2 (FLS2) with its co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1), and this function is inhibited by the FER ligand RAPID ALKALANIZATION FACTOR 23 (RALF23). Here, we show that FER regulates the plasma membrane nanoscale organization of FLS2 and BAK1. Our study demonstrates that akin to FER, leucine-rich repeat (LRR) extensin (LRXs) proteins contribute to RALF23 responsiveness, regulate BAK1 nanoscale organization and immune signaling. Furthermore, RALF23 perception leads to rapid modulation of FLS2 and BAK1 nanoscale organization and its inhibitory activity on immune signaling relies on FER kinase activity. Our results suggest that perception of RALF peptides by FER and LRXs actively modulates the plasma membrane nanoscale landscape to regulate cell surface signaling by other receptor kinases.

plant biology↗