Principles of branch dynamics governing shape characteristics of cerebellar Purkinje cell dendrites

Abstract

Neurons develop dendritic arbors in cell type-specific patterns. Using growing Purkinje cells in culture as a model, we performed a long-term time-lapse observation of dendrite branch dynamics to understand the rules that govern the characteristic space-filling dendrites. We found that dendrite architecture was sculpted by a combination of reproducible dynamic processes, including constant tip elongation, stochastic terminal branching, and retraction triggered by contacts between growing dendrites. Inhibition of protein kinase C/protein kinase D signaling prevented branch retraction and significantly altered the characteristic morphology of long proximal segments. A computer simulation of dendrite branch dynamics using simple parameters from experimental measurements reproduced the time-dependent changes in the dendrite configuration in live Purkinje cells. Furthermore, perturbation analysis to parameters in silico validated the important contribution of dendritic retraction in the formation of the characteristic morphology. We present an approach using live imaging and computer simulations to clarify the fundamental mechanisms of dendrite patterning in the developing brain.

Dendrite Self-Avoidance Requires Cell-Autonomous Slit/Robo Signaling in Cerebellar Purkinje Cells

“…Interestingly, in C. elegans , the secreted molecule Netrin/UNC-6 was also proposed to mediate recognition, but via a capture-and-display mechanism involving two distinct receptors expressed on neighboring dendrites (Smith et al, 2012). In both cases, the molecular interaction fits well with the contact-dependent nature of self-avoidance as revealed by live imaging (Fujishima et al, 2012; Liu and Halloran, 2005; Montague and Friedlander, 1991; Sagasti et al, 2005; Sdrulla and Linden, 2006; Smith et al, 2012). …”

“…Slit2 expressed by PCs may associate with dendrites and serve as repulsive barriers to sister branches (Fujishima et al, 2012; Sdrulla and Linden, 2006). Thus, we asked whether Slit proteins could repel PC dendrites.…”

“…Initially discovered in leech mechanosensory neurons (Kramer and Kuwada, 1983), self-avoidance has been found for both axons and dendrites in a wide range of invertebrate and vertebrate neurons (Fujishima et al, 2012; Hughes et al, 2007; Liu and Halloran, 2005; Matthews et al, 2007; Montague and Friedlander, 1991; Sagasti et al, 2005; Sdrulla and Linden, 2006; Soba et al, 2007). Recent invertebrate studies have identified a number of cell-surface molecules that are required cell-autonomously for establishing non-overlapping dendrites or axons in a roughly two dimensional (2D) plane.…”

Emerging roles of protocadherins: from self-avoidance to enhancement of motility

“…It is also important to identify cytoplasmic factors that interact with clustered protocadherins in order to investigate the molecular mechanisms of how these protocadherins control neurite patterning, including selfavoidance. Live imaging of neurites undergoing self-avoidance would be helpful in order to elucidate the cellular mechanisms underlying this process, which has been successfully used to analyze the avoidance of Purkinje cell dendrites (Fujishima et al, 2012). It is also crucial for our global understanding of the functions of this molecular group to determine whether and how the Pcdhcdependent self-avoidance is related to its reported role in cell survival.…”

Coordinate control of terminal dendrite patterning and dynamics by the membrane protein Raw

“…Many organelles are selectively deployed in dendrites, including a satellite secretory pathway containing endoplasmic reticulum and Golgi outposts; the number and location of these organelles locally influences dendrite growth and dynamics (Aridor et al, 2004;Gardiol et al, 1999;Horton and Ehlers, 2003;Ye et al, 2007). In highly branched dendrite arbors, for example cerebellar Purkinje neurons and insect sensory neurons, major dendrites and terminal dendrites have distinct cytoskeletal compositions and growth properties (Fujishima et al, 2012;Jinushi-Nakao et al, 2007). Finally, dendrite arbors often contain functionally distinct domains as well.…”