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000619953 1001_ $$aHan, Yuhao$$b0
000619953 245__ $$aUnveiling the cell biology of hippocampal neurons with dendritic axon origin
000619953 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2025
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000619953 520__ $$aIn mammalian axon-carrying–dendrite (AcD) neurons, the axon emanates from a basal dendrite, instead of the soma, to create a privileged route for action potential generation at the axon initial segment (AIS). However, it is unclear how such unusual morphology is established and whether the structure and function of the AIS in AcD neurons are preserved. By using dissociated hippocampal cultures as a model, we show that the development of AcD morphology can occur prior to synaptogenesis and independently of the in vivo environment. A single precursor neurite first gives rise to the axon and then to the AcD. The AIS possesses a similar cytoskeletal architecture as the soma-derived AIS and similarly functions as a trafficking barrier to retain axon-specific molecular composition. However, it does not undergo homeostatic plasticity, contains lesser cisternal organelles, and receives fewer inhibitory inputs. Our findings reveal insights into AcD neuron biology and underscore AIS structural differences based on axon onset.
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000619953 7001_ $$00000-0001-6922-7017$$aHacker, Daniela$$b1
000619953 7001_ $$00009-0004-3840-5529$$aDonders, Bronte Catharina$$b2
000619953 7001_ $$00009-0006-0592-3519$$aParperis, Christopher$$b3
000619953 7001_ $$0P:(DE-H253)PIP1087856$$aThuenauer, Roland$$b4
000619953 7001_ $$00000-0002-2957-2032$$aLeterrier, Christophe$$b5
000619953 7001_ $$00000-0002-4788-2691$$aGrünewald, Kay$$b6$$eCorresponding author
000619953 7001_ $$00000-0001-7646-1346$$aMikhaylova, Marina$$b7$$eCorresponding author
000619953 773__ $$0PERI:(DE-600)1421310-2$$a10.1083/jcb.202403141$$gVol. 224, no. 1, p. e202403141$$n1$$pe202403141$$tThe journal of cell biology$$v224$$x0021-9525$$y2025
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