Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room

Abstract

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.

A crabs' high‐order brain center resolved as a mushroom body‐like structure

“…Adult neurogenesis is a highly plastic and highly restricted mechanism within central nervous systems. This process is mainly limited to two structures in invertebrates and vertebrates (olfactory neuropils and mushroom bodies/hemiellipsoid bodies or olfactory bulbs and hippocampus respectively) (Becker, 2017; Beltz & Benton, 2017; Beltz, Brenneis, & Benton, 2016; Cayre et al, 1996; Hansen & Schmidt, 2004; Kempermann, 2012; Schmidt, 1997, 2014; Sullivan et al, 2007, b; Sullivan & Beltz, 2005a). The incorporation of new neurons may be an important component in the functional role of these structures, not only in the sense that it provides more elements to the system but also increases the variety of elements with different functional properties (e.g., excitability, less inhibition, synaptic plasticity; Becker, 2017; Kempermann, 2012).…”

Adult neurogenesis in crayfish: Origin, expansion, and migration of neural progenitor lineages in a pseudostratified neuroepithelium

“…These parallels between the life‐long neurogenic mechanisms of two taxa as phylogenetically distant as crayfish and mammals may serve as another illustration of how evolution independently generates similar solutions when faced with similar challenges. Seen from this perspective, the recently discovered novel mode of NP pool replenishment via integration and neural differentiation of hemocytes in the crayfish DPS (Benton et al, ) may well represent a more ubiquitous pathway than originally appreciated and thus inform the future direction of studies on mammalian systems (see Beltz et al, ; Beltz, Brenneis, & Benton, for further discussion).…”

Adult neurogenesis in the central olfactory pathway of dendrobranchiate and caridean shrimps: New insights into the evolution of the deutocerebral proliferative system in reptant decapods

“…Despite these controversial findings concerning the mechanisms driving adult neurogenesis, in most decapod crustaceans studied so far fibrous migratory streams from the neurogenic niche serve as pathways from which these neuronal precursors, mediated by dynein‐binding proteins (Zhang et al, ), travel toward proliferation zones which are associated with soma clusters of the olfactory system. Within these proliferation zones, the neuronal progenitor cells proliferate and give rise to new neurons of the olfactory pathway (reviews Sandeman et al, ; Benton et al, ; Sandeman et al, ; Beltz et al, ). Pulse‐chase experiments with proliferation markers such as BrdU in clawed lobsters, spiny lobsters and crayfish have provided strong evidence that these newly born neurons within the proliferation zones survive and are integrated into the existing circuitry of the central olfactory pathway (Harzsch et al, ; Schmidt, ; Sullivan and Beltz, ; Sullivan et al, ; b; Kim et al, ).…”

“…Pulse‐chase experiments with proliferation markers such as BrdU in clawed lobsters, spiny lobsters and crayfish have provided strong evidence that these newly born neurons within the proliferation zones survive and are integrated into the existing circuitry of the central olfactory pathway (Harzsch et al, ; Schmidt, ; Sullivan and Beltz, ; Sullivan et al, ; b; Kim et al, ). The rate of mitosis as well as survival and differentiation of the newly born cells within the crustacean deutocerebrum are modulated, for example, by the neuromodulator serotonin, rearing conditions (“impoverished versus enriched environment”), circadian and seasonal effects, social interactions and locomotory activity (reviews Sandeman et al, ; Benton et al, ; Schmidt, ; Sandeman et al, ; Beltz et al, ).…”

“…In crayfish, the neurogenic niche is composed of a group of cells with glial characteristics and a central cavity which is associated with the vascular system (Sullivan et al, ; b; Sandeman et al, ; Chaves da Silva et al, 2012). It has been suggested that the crayfish niche does not house a population of self‐renewing stem cells, but that it is an open system in which progenitor cells of hematopoietic origin are recruited and are then transformed into a neuronal fate (review Benton et al, ; Benton et al, ; Beltz et al, ). On the contrary, an adult neuroblast which is a neural stem cell‐like progenitor cell that gives rise to neuronal progenitor cells by repeated asymmetrical divisions (self‐renewal) was suggested to reside in the neurogenic niche of the spiny lobster Panulirus argus (Schmidt ).…”