Developing neuronal axons are directed by chemical and physical signals toward a myriad of target cells. According to current dogma, the resulting network architecture is critically shaped by electrical interconnections, the synapses; however, key mechanisms translating neuronal interactions into neuronal growth behavior during network formation are still unresolved. To elucidate these mechanisms, we examined neurons interfacing nanopatterned substrates and compared them to natural interneuron interactions. We grew similar neuronal populations under three connectivity conditions, (1) the neurons are isolated, (2) the neurons are interconnected, and (3) the neurons are connected only to artificial substrates, then quantitatively compared both the cell morphologies and the transcriptome-expression profiles. Our analysis shows that whereas axon-guidance signaling pathways in isolated neurons are predominant, in isolated neurons interfacing nanotopography, these pathways are downregulated, similar to the interconnected neurons. Moreover, in nanotopography, interfacing neuron genes related to synaptogenesis and synaptic regulation are highly expressed, that is, again resembling the behavior of interconnected neurons. These molecular findings demonstrate that interactions with nanotopographies, although not leading to electrical coupling, play a comparable functional role in two major routes, neuronal guidance and network formation, with high relevance to the design of regenerative interfaces.
|Number of pages||9|
|State||Published - 13 Mar 2019|
Bibliographical noteFunding Information:
This work was supported by the Israel Science Foundation Individual grant #1053/15 (O.S.) and by the Levi Eshkol Fellowship from The Israeli Ministry of Science, Technology and Space (K.B.). We thank the FIB/SEM center in the Bar Ilan Institute of Nanotechnology and Advanced Materials (BINA) for assistance with the high-resolution imaging. We thank Ganit Eran Indech for the fabrication of some of the nanopatterned substrates.
© Copyright 2019 American Chemical Society.
- Neuronal growth
- brain machine interface
- gene expression