Medullary bone in male budgerigars (Melopsittacus undulatus) with testicular neoplasms

Medullary bone is a calcium-rich, labile bone normally occurring in female birds with each egg-laying cycle. The stimulus for formation of medullary bone is, in part, the cyclic increase in serum estrogens produced by preovulatory ovarian follicles. Increased bone density due to formation of medullary bone, particularly in pneumatic bones, has been termed polyostotic hyperostosis, even if physiologic. This study investigated the formation of medullary bone in nonpneumatic (femur) and pneumatic (humerus) bones in sexually mature male budgerigars submitted for autopsy. Of the 21 sexually mature male budgerigars submitted for autopsy, 7 (33%) had medullary bone in 1 or more bones examined. All 7 male budgerigars with medullary bone had a testicular neoplasm, which was morphologically consistent with a testicular sustentacular cell tumor, seminoma, or interstitial cell tumor. Medullary bone was not present in the 14 cases with other diseases. Medullary bone formation in pneumatic and nonpneumatic bones can occur in male budgerigars with testicular neoplasms. Radiographic increases in medullary bone density, particularly in the humerus, could provide antemortem indication of testicular neoplasia in male budgerigars.

Smad4 controls proliferation of interstitial cells in the neonatal kidney

Expansion of interstitial cells in the adult kidney is a hallmark of chronic disease, whereas their proliferation during fetal development is necessary for organ formation. An intriguing difference between adult and neonatal kidneys is that the neonatal kidney has the capacity to control interstitial cell proliferation when the target number has been reached. In this study, we define the consequences of inactivating the TGFβ/Smad response in the interstitial cell lineage. We find that pathway inactivation through loss of Smad4 leads to over-proliferation of interstitial cells regionally in the kidney medulla. Analysis of markers for BMP and TGFβ pathway activation reveals that loss of Smad4 primarily reduces TGFβ signaling in the interstitium. While TGFβ signaling is reduced in these cells, marker analysis shows that Wnt/β-catenin signaling is increased. Our analysis supports a model in which Wnt/β-catenin mediated proliferation is attenuated by TGFβ/Smad to ensure that proliferation ceases when the target number of interstitial cells has been reached in the neonatal medulla.

How Many Cell Types Are in the Kidney and What Do They Do?

The kidney maintains electrolyte, water, and acid-base balance, eliminates foreign and waste compounds, regulates blood pressure, and secretes hormones. There are at least 16 different highly specialized epithelial cell types in the mammalian kidney. The number of specialized endothelial cells, immune cells, and interstitial cell types might even be larger. The concerted interplay between different cell types is critical for kidney function. Traditionally, cells were defined by their function or microscopical morphological appearance. With the advent of new single-cell modalities such as transcriptomics, epigenetics, metabolomics, and proteomics we are entering into a new era of cell type definition. This new technological revolution provides new opportunities to classify cells in the kidney and understand their functions. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The homeobox gene, TGIF1, is required for chicken ovarian cortical development and generation of the juxtacortical medulla

During early embryogenesis in amniotic vertebrates, the gonads differentiate into either ovaries or testes. The first cell lineage to differentiate gives rise to the supporting cells; Sertoli cells in males and pre-granulosa cells in females. These key cell types direct the differentiation of the other cell types in the gonad, including steroidogenic cells. The gonadal surface epithelium and the interstitial cell populations are less well studied, and little is known about their sexual differentiation programs. Here, we show the requirement of the homeobox transcription factor gene TGIF1 for ovarian development in the chicken embryo. TGIF1 is expressed in the two principal ovarian somatic cell populations, the cortex and the pre-granulosa cells of the medulla. TGIF1 expression is associated with an ovarian phenotype in estrogen-mediated sex reversal experiments. Targeted mis-expression and gene knockdown indicate that TGIF1 is required, but not sufficient, for proper ovarian cortex formation. In addition, TGIF1 is identified as the first known regulator of juxtacortical medulla development. These findings provide new insights into chicken ovarian differentiation and development, specifically cortical and juxtacortical medulla formation.