Grant: Project Grant

The human hypothalamus is only about the size of an almond and yet, it is very important to our survival. Indeed, the hypothalamus is essential for regulating key physiologies such as when to eat, sleep, drink, reproduce, shiver, and even love. To control these physiologies, the hypothalamus acts as a thermostat, first by sensing cues and then eliciting a response via its many neurons. Interestingly, even during embryonic development, the hypothalamus is still responsive to its environment. Microglia are another type of sensing cell in the brain but instead of responding to external cues, microglia respond to internal ones. For example, microglia are tasked with detecting injury and trying to repair it, as well as identifying unnecessary debris (e.g., dying cells) and clearing them away. Recent studies are starting to show that microglia also influence fetal brain development. Our own work has demonstrated a unique role for microglia in the developing hypothalamus. We have discovered that microglia in the embryonic hypothalamus are particularly activated, clustering around a discrete niche of the dorsal third ventricle. We showed that hypothalamic microglia interact with progenitors and can influence normal developmental programs. Consistent with these findings, elimination of microglia during gestation caused newborn pups to be born obese, strongly supporting a role for microglia in hypothalamic development. From these data and others, we hypothesize that microglia communicate with hypothalamic RGCs to influence development, particularly tanycytes. In this proposal, we will test the intriguing notion that cells whose primary purpose is to sense insults (e.g., microglia) are used to establish the key brain region essential to sensing homeostatic cues throughout life.