An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression.

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.

Single-cell analysis of early progenitor cells that build coronary arteries.

Arteries and veins are specified by antagonistic transcriptional programs. However, during development and regeneration, new arteries can arise from pre-existing veins through a poorly understood process of cell fate conversion. Here, using single-cell RNA sequencing and mouse genetics, we show that vein cells of the developing heart undergo an early cell fate switch to create a pre-artery population that subsequently builds coronary arteries. Vein cells underwent a gradual and simultaneous switch from venous to arterial fate before a subset of cells crossed a transcriptional threshold into the pre-artery state. Before the onset of coronary blood flow, pre-artery cells appeared in the immature vessel plexus, expressed mature artery markers, and decreased cell cycling. The vein-specifying transcription factor COUP-TF2 (also known as NR2F2) prevented plexus cells from overcoming the pre-artery threshold by inducing cell cycle genes. Thus, vein-derived coronary arteries are built by pre-artery cells that can differentiate independently of blood flow upon the release of inhibition mediated by COUP-TF2 and cell cycle factors.

Architectonics of male amygdala.

The aim of this manuscript is to demonstrate that the known hormonally driven development of the male amygdalae, requires the vital use of stored memory in order that they are able to complete their recognised full structural architectonics. The hippocampus and the entorhinal cortex are strongly involved in the reception of testosterone which is the responsible hormone. The transfer of testosterone into memory and the mode of consolidation and storage of that memory are discussed. In regard to this activity, there have been suggestions concerning the possible effect of immune processes and also epigenesis and these are discussed. Finally, the controlled transfer to the male amygdala and the anabolic effect upon it are elucidated. The understanding of the hippocampal memory system is challenged by new evidence that has arisen.

The interrelationship between genes, microprolactinoma and male homosexuality.

This hypothesis clearly proposes the true and previously undiscovered cause of male homosexuality or bisexuality and in most cases the predictability in infancy of the development of this sexuality in adulthood. It is based on compelling new evidence which has accumulated over many years. The fetal and neonatal periods are of the utmost importance in human development because they encompass critical periods which must be adhered to, for normal development. Biological variations may occur during these times, without implying the process of disease. This paper takes into account new paediatric hormonal and other evidence which has accumulated in the past two decades concerning the causation of male homosexuality or bisexuality. It includes indirect genetic influence which has now been shown to be present. It also includes the implications of infant male breast development in regard to sexuality. It is asserted that the major cause of male homosexuality is due to failure of masculinisation of the male brain due to temporary but critical prolactin secretion from microprolactinoma present in their pituitary glands. Genes appear to be involved in the production of these tumours and sometimes in their demise. The assessment of their numbers at any one time in infancy has not been correctly addressed. Secondly, there is absolutely compulsive evidence concerning increased male infant breast development and the true nature of "Witch's Milk" and how it is produced and the profound implications of its presence in male neonates. It adds much persuasion to the causation of male homosexuality as enunciated in this paper. Measurement of testosterone levels at exactly and precisely the right time, are able to predict homosexual or bisexual development in adults. This knowledge would be of great help to parents.