The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders.
KEY WORDS: Cell-intrinsic driver, Dendrite development, Dendrite morphogenesis, Dendrite patterning, Transcription factor, Ubiquitin ligases
IntroductionWith their tremendous complexity and diversity, dendrites are one of nature's architectural masterpieces. More than a century ago, Ramón y Cajal proposed an important role for dendrites (referred to at that time as protoplasmic processes) as specialized morphological structures that receive neuronal input (Ramón y Cajal, 1995). Further studies using a variety of neuronal cell types (see Glossary, Box 1) have vastly improved our understanding of dendrite development (Scott and Luo, 2001;Grueber and Jan, 2004). The development of new approaches for studying dendrite morphogenesis (see Box 2) has led to the view that axons and dendrites work in concert to define neuronal connectivity. A key concept that has emerged from such functional studies is that the particular shapes of dendrites are intimately tied to the proper wiring of neuronal circuits and their function (Häusser et al., 2000;Parrish et al., 2007b;Branco et al., 2010;Branco and Häusser, 2011;Gidon and Segev, 2012; Lavzin et al., 2012).Prior to the elaboration of dendrites, neurons undergo axodendritic polarization, whereby the morphologically and functionally distinct axonal and dendritic compartments (see Box 3) are specified. In most neurons, including retinal ganglion neurons, forebrain pyramidal neurons and cerebellar granule neurons, the generation of an axon precedes the development and elaboration of dendrites (Ramón y Cajal, 1995). Although individual neuronal cell Anterodorsal and lateral projection neurons (aPNs and lPNs). These neurons of the Drosophila antennal lobe are crucial for olfactory processing. They receive excitatory input from olfactory receptor neurons in glomeruli and transmit signals to the mushroom body and lateral horn. Cerebellar granule neurons. The most numerous neurons of the brain, these offer an ideal system for biochemical, morphological and physiological studi...