title: Protocadherins branch out: Multiple roles in dendrite development.
abstract: The proper formation of dendritic arbors is a critical step in neural circuit formation, and as such defects in arborization are associated with a variety of neurodevelopmental disorders. Among the best gene candidates are those encoding cell adhesion molecules, including members of the diverse cadherin superfamily characterized by distinctive, repeated adhesive domains in their extracellular regions. Protocadherins (Pcdhs) make up the largest group within this superfamily, encompassing over 80 genes, including the ∼60 genes of the α-, β-, and γ-Pcdh gene clusters and the non-clustered δ-Pcdh genes. An additional group includes the atypical cadherin genes encoding the giant Fat and Dachsous proteins and the 7-transmembrane cadherins. In this review we highlight the many roles that Pcdhs and atypical cadherins have been demonstrated to play in dendritogenesis, dendrite arborization, and dendritic spine regulation. Together, the published studies we discuss implicate these members of the cadherin superfamily as key regulators of dendrite development and function, and as potential therapeutic targets for future interventions in neurodevelopmental disorders.
authors: a Department of Biology ; Neuroscience Graduate Program; University of Iowa ; Iowa City , IA USA.
authors: Austin B
authors: AB
authors: Keeler
authors: Michael J
authors: MJ
authors: Molumby
authors: Joshua A
authors: JA
authors: Weiner
mesh_terms: D000818:Animals; D015820:Cadherins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules
keywords: CNR, Cadherin related neuronal receptor; CTCF, CCCTC-binding factor; CaMKII, Ca2+/calmodulin-dependent protein kinase II.; Celsr, Cadherin EGF LAG 7-pass G-type receptor 1; DSCAM, Down syndrome cell adhesion molecule; Dnmt3b, DNA (cytosine-5-)-methyltransferase 3 β; Ds, Dachsous; EC, extracellular cadherin; EGF, Epidermal growth factor; FAK, Focal adhesion kinase; FMRP, Fragile X mental retardation protein; Fj, Four jointed; Fjx1, Four jointed box 1; GPCR, G-protein-coupled receptor; Gogo, Golden Goal; LIM domain, Lin11, Isl-1 & Mec-3 domain; MARCKS, Myristoylated alanine-rich C-kinase substrate; MEF2, Myocyte enhancer factor 2; MEK3, Mitogen-activated protein kinase kinase 3; PCP, planar cell polarity; PKC, Protein kinase C; PSD, Post-synaptic density; PYK2, Protein tyrosine kinase 2; Pcdh; Pcdh, Protocadherin; RGC, Retinal ganglion cell; RNAi, RNA interference; Rac1, Ras-related C3 botulinum toxin substrate 1; S2 cells, Schneider 2 cells; SAC, starburst amacrine cell; TAF1, Template-activating factor 1; TAO2β, Thousand and one amino acid protein kinase 2 β; TM, transmembrane; arborization; atypical cadherin; branching; cadherin superfamily; cell adhesion; da neuron, dendritic arborization neuron; dendritic; dendritic spine; dendritogenesis; fmi, Flamingo; md neuron, multiple dendrite neuron; neural circuit formation; p38 MAPK, p38 mitogen-activated protein kinase; self avoidance; synaptogenesis