[
Studies of History & Philosophy of Science,
1998]
In 1963, just a year after the researchers of the Medical Research Council (MRC) Unit of Molecular Biology in Cambridge, joined by some other research groups, has moved from various scattered and makeshift buildings in the courtyard of the Physics Department to a lavishly funded four-storey laboratory, B. Lush, the Principal Medical Officer of the MRC, came to inquire about their plans for future expansion. He indicated that the MRC wished to build the laboratory up to what the principal researchers considered its 'final size' until their retirement, which meant planning ahead for at least 15 years. This surprising move was doubtless prompted by the recent award of the Nobel Prize to three members of the laboratory, Max Perutz, John Kendrew and Francis Crick, for their work on the molecular structure of proteins and nucleic acids. The triple award had propelled the new Laboratory of Molecular Biology into the limelight, and the MRC was interested in securing optimal research conditions for this prestigious group of researchers.
[
Front Cell Dev Biol,
2022]
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, <i>in vivo</i> approaches using <i>C. elegans</i> and <i>D. melanogaster,</i> as well as <i>in situ</i> 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.