Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus

Abstract

The adult hypothalamus regulates many physiological functions and homeostatic loops, including growth, feeding and reproduction. In mammals, the hypothalamus derives from the ventral diencephalon where two distinct ventricular proliferative zones have been described. Although a set of transcription factors regulating the hypothalamic development has been identified, the exact molecular mechanisms that drive the differentiation of hypothalamic neural precursor cells (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully disclosed. Neurogenesis has been also reported in the adult hypothalamus at the level of specific niches located in the ventrolateral region of ventricle wall, where NPCs have been identified as radial glia-like tanycytes. Here we review the molecular and cellular systems proposed to support the neurogenic potential of developing and adult hypothalamic NPCs. We also report new insights on the mechanisms by which adult hypothalamic neurogenesis modulates key functions of this brain region. Finally, we discuss how environmental factors may modulate the adult hypothalamic neurogenic cascade.

Keywords: adult stem cells; hypothalamus; neural progenitor cells; neural stem cell (NSC); neurogenesis; tanycytes.

Figure 1

Differentiation of hypothalamic NPCs during development. (A) At E12.5–14.5 newborn neuroblasts are progressively specified and start the production of specific neurohormones while migrating toward the appropriate hypothalamic nucleus. At later embryonic stage (E16–18) ciliated and non-ciliated ependymal cells are generated and take place along the 3rd ventricle wall. Finally, tanycytes are generated during perinatal period and in the first post-natal days. (B) AC1 cells, a NPC population established from fetal hypothalamus. These cells display typical NPC and hypothalamic markers such Sox2 and Nestin respectively (left panel). If prompted to differentiate, they generate mature hypothalamic neurons. (C) Schematic diagram reporting the transcription factors expressed by AC1 cells during proliferation and their conversion into specific neurohormone-secreting neuronal subtypes (see Cariboni et al., 2014).

Figure 2

Schematic representation of the NPC populations existing in the adult hypothalamic niche. The medial part of the 3V contains α1-tanycytes and proliferative α2-tanycytes that take contact with the VMN and ARN nuclei respectively. β-tanycytes reside on the floor of the 3V and in strict association with the hypothalamic-pituitary portal system. VMN: ventromedial nucleus; ARN: arcuate nucleus; 3V: 3rd ventricle; ME: median eminence.