What Scientists Did This Summer

Graduate Division

Breast biology: not your average organ development

The breast, or mammary gland, is a unique organ: it’s the only one that develops predominantly after birth – during puberty – in an organism with a fully-developed immune system. Early development trains the immune system to distinguish between “self” and “non-self” in an effort to prepare for all sorts of infectious attacks throughout life. Imagine the immune system’s surprise when, after a full childhood of successfully fighting off diseases, it notices a completely new organ forming right under its nose! Anyone who spent time in Yosemite this summer will know that to leave in one piece, you don’t startle the baby bear, because mama bear is watching. Similarly, if you startle the sentinel immune cells by suddenly growing a whole new organ, the adaptive immune system rolls in and starts to do damage.

This is a fabulous new fundamental discovery that came out of Zena Werb’s lab at UCSF this summer, published in Developmental Cell. Using beautiful fluorescent images and videos of the developing mouse mammary gland, this study reveals a visually stunning environment of monocytic-like cells crawling around the growing and branching mammary epithelial tree. These cells take samples of the epithelium and present them to T helper cells, stimulating them to release growth-inhibiting cytokines (for example, interferon gamma). The result was inhibited growth of luminal mammary epithelial cells. Follow up experiments using mice deficient for interferon gamma signaling showed accelerated branching of the breast’s ductal tree – proving that growth-inhibiting signals sent by immune cells are necessary for regulating appropriate growth and development of the breast.

Interestingly, while T cells associated in the developing breast predominantly expressed growth-inhibiting signals, breast tumor-associated T cells are known to be skewed toward immune-suppressive and tumor-facilitating signaling. Thus, a switch occurs in the surrounding immune response when breast cells become malignant. It’s possible that the experience mammary epithelial cells have interacting with T cells could poise them to develop an escape mechanism more easily when they become cancerous – for example, by blocking interferon gamma signaling. This could potentially explain why the breast is such a cancer-prone organ. While the cancer connection still remains speculation, what this study definitely shows is that the immune system is involved in the development of a non-immune organ, and that is a fundamental discovery of basic biology that doesn’t happen too often anymore.

Sources: Developmental Cell

A new human ancestor

Homo naledi: a new extinct member of the Homo genus was discovered in the Dinaledi Chamber of the Rising Star cave system in South Africa in an unusually large collection of 15 individual fossilized skeletons. In fact, it was likely a burial site, a practice that until now was thought to be a strictly modern-human one. Two papers in eLife from groups at the University of Witwatersrand led by Lee Berger supported by the National Geographic describe this jackpot find and the physical characteristics of the human ancestor.

The species appears to have been a gradient of primitive and modern features from top to bottom: tiny primitive heads, primitive ape-like shoulders good for climbing, modern hands but with curved fingers, and modern feet. “The message we’re getting is of an animal right on the cusp of the transition from Australopithecus to Homo,” said Berger of these tall individuals with tiny heads. Unfortunately, because the bones were embedded in shallow soil or just scattering the cave floor, they can’t easily be dated, so it’s not yet clear where they fit into the timeline of human evolution.

Sources: eLife, eLife, National Geographic