A Cold-Blooded View on Adult Neurogenesis

Abstract

During brain development, highly complex and interconnected neural circuits are established. This intricate wiring needs to be robust to faithfully perform adult brain function throughout life, but at the same time offer room for plasticity to integrate new information. In the mammalian brain, adult-born neurons are produced in restricted niches harboring neural stem cells. In the fruit fly Drosophila, low-level adult neurogenesis arising from a dispersed population of neural progenitors has recently been detected in the optic lobes. Strikingly, these normally quiescent neural stem cells proliferate upon brain injury and produce new neurons for brain regeneration. Here, we review adult neurogenesis in crustaceans and insects and highlight that neurogenesis in the visual system is prominent in arthropods, but its role and underlying mechanisms are unclear. Moreover, we discuss how the study of damage-responsive progenitor cells in Drosophila may help to understand robust regenerative neurogenesis and open new avenues to enhance brain repair after injury or stroke in humans.

Keywords: Drosophila; activation of quiescent stem cells; adult neural stem cells; adult neurogenesis in arthropods; regenerative neurogenesis.

Figure 1

Neurogenic zones in crustacean and insect species. (A) Adult neurogenesis in crayfish occurs in the medulla (med) of the optic lobe (OL), the hemiellipsoid body (HEB) and in cluster (CL) 9 and 10 adjacent to the olfactory lobe. The red circle below the clusters designates the niche. Circulating hemocytes in the blood enter the niche in the brain via underlying blood vessels (BVs). The progeny of these hemocyte-derived stem cells (hSCs), called secondary precursors (2nd Pcs) migrate along streams to the proliferation clusters, where they divide and differentiate into olfactory interneurons. (B) In crickets, adult-proliferating cells are found in the optic lobes and the cortex of the adult mushroom bodies. New neurons arise from mushroom body (MB) neuroblasts, which divide asymmetrically to self-renew and produce a ganglion mother cell (GMC), which in turn divides to form two neurons. KC, Kenyon cells. (C) Low-level adult neurogenesis occurs in the outer medulla of fruit fly. Adult-born neurons derive from symmetric divisions of neural precursors and likely intermediate proliferating cells (IPCs). Neurogenic zones are shaded in red. Light red indicates proliferating zones, where no published images are available.

Figure 2

Injury-induced neurogenesis in the adult fly brain. (A) Traumatic brain injury paradigm in Drosophila: Stab lesions are performed with a thin metal filament to injure the right optic lobe (ROL). (B) Scheme depicting the retina and neuropils of the optic lobe. The eye is lesioned to the level of the medulla. La, Lamina; Med, Medulla; L, Lobula; Lop, Lobular plate. (C) Injury leads to activation and proliferation of quiescent adult neural progenitor cells, which give rise to new neurons, likely involving generation of a type of intermediate proliferating cell (IPC). SC, Stem cells.