The Evolutionary Assembly of Neuronal Machinery

Abstract

Neurons are highly specialized cells equipped with a sophisticated molecular machinery for the reception, integration, conduction and distribution of information. The evolutionary origin of neurons remains unsolved. How did novel and pre-existing proteins assemble into the complex machinery of the synapse and of the apparatus conducting current along the neuron? In this review, the step-wise assembly of functional modules in neuron evolution serves as a paradigm for the emergence and modification of molecular machinery in the evolution of cell types in multicellular organisms. The pre-synaptic machinery emerged through modification of calcium-regulated large vesicle release, while the postsynaptic machinery has different origins: the glutamatergic postsynapse originated through the fusion of a sensory signaling module and a module for filopodial outgrowth, while the GABAergic postsynapse incorporated an ancient actin regulatory module. The synaptic junction, in turn, is built around two adhesion modules controlled by phosphorylation, which resemble septate and adherens junctions. Finally, neuronal action potentials emerged via a series of duplications and modifications of voltage-gated ion channels. Based on these origins, key molecular innovations are identified that led to the birth of the first neuron in animal evolution.

Insm1-expressing neurons and secretory cells develop from a common pool of progenitors in the sea anemoneNematostella vectensis

“…The electrical excitability and conduction in muscle cells is based on the same types of voltage-gated sodium and calcium channels as that of neurons, whereas the release of synaptic vesicles involves many proteins associated with the vesicle and plasma membrane, respectively, that also function in vesicle release from non-neural secretory and endocrine cells. The evolution of neurons thus likely resulted from the elaboration of different pre-existing cellular modules (Arendt, 2020; Brunet and Arendt, 2016; Burkhardt and Sprecher, 2017; Kristan, 2016; Liebeskind et al, 2017; Moroz, 2009; Varoqueaux and Fasshauer, 2017). Since the presence of the constituents of these different cellular modules within the same cell requires their co-ordinated expression, analysing the gene regulatory program and the developmental origin of neurons in different species can provide valuable insights into the evolutionary relationship between neurons and other cell types.…”

A comprehensive series of temporal transcription factors in the fly visual system

“…Recent studies have highlighted key aspects of the evolution of the “nuts and bolts” of a functional neuron, such as the molecules of the pre- and post-synaptic machinery 59 (i.e. how neurons evolved).…”

Choanoflagellates and the ancestry of neurosecretory vesicles

“…Even though animal synapses have been extensively studied through several decades, their evolutionary origin is still unresolved [6][7][8][9][10]. However, reconstructing the evolutionary origin of the first synapses is an important landmark to understand how cognitive processes in single-celled organisms were altered and adapted to function in multicellular organisms.…”