Perspectives on Mechanisms Supporting Neuronal Polarity From Small Animals to Humans

Abstract

Axon-dendrite formation is a crucial milestone in the life history of neurons. During this process, historically referred as “the establishment of polarity,” newborn neurons undergo biochemical, morphological and functional transformations to generate the axonal and dendritic domains, which are the basis of neuronal wiring and connectivity. Since the implementation of primary cultures of rat hippocampal neurons by Gary Banker and Max Cowan in 1977, the community of neurobiologists has made significant achievements in decoding signals that trigger axo-dendritic specification. External and internal cues able to switch on/off signaling pathways controlling gene expression, protein stability, the assembly of the polarity complex (i.e., PAR3-PAR6-aPKC), cytoskeleton remodeling and vesicle trafficking contribute to shape the morphology of neurons. Currently, the culture of hippocampal neurons coexists with alternative model systems to study neuronal polarization in several species, from single-cell to whole-organisms. For instance, in vivo approaches using C. elegans and D. melanogaster, as well as in situ imaging in rodents, have refined our knowledge by incorporating new variables in the polarity equation, such as the influence of the tissue, glia-neuron interactions and three-dimensional development. Nowadays, we have the unique opportunity of studying neurons differentiated from human induced pluripotent stem cells (hiPSCs), and test hypotheses previously originated in small animals and propose new ones perhaps specific for humans. Thus, this article will attempt to review critical mechanisms controlling polarization compiled over decades, highlighting points to be considered in new experimental systems, such as hiPSC neurons and human brain organoids.

On the way back from 3D to 2D: Chitosan promotes adhesion and development of neuronal networks onto culture supports

“…3A. The results showed that on CHI1 there was an extension in the first hours and then a retraction, but this behavior is typical of minor processes during Stage 2 (12-24 h) (Miyata et al, 2005) that precedes Stage 3 in which a minor process begins to grow rapidly and transforms into an axon (symmetry break) (Wilson et al, 2022).…”

Dual spatio-temporal regulation of axon growth and microtubule dynamics by RhoA signaling pathways

“…Studies on cultured hippocampal and cortical neurons that develop in situ have established that the generation of an axon from a rather symmetric array of short and highly dynamic undifferentiated neurites is one of the early events underlying the establishment of morphological polarity (Caceres et al, 2012; Funahashi et al, 2014; Wilson et al, 2022). Current evidence favors the view that an increase in actin dynamics and growth cone size selects a minor neurite to become the axon (Bradke and Dotti, 1997, 1999; Kunda et al, 2001).…”