Genetic Control of Neuronal Architecture
Dendrite, Neuron shape, Neural stem cell
Our aim is to investigate, at the level of an individual nascent neuron, how differentiation pathways are initiated and directed to create diversity in neuron form and function. Nervous system function is dependent upon carefully organized and intricate circuit architectures that are in turn assembled from a wide variety of neuron classes, each of which with characteristic morphological and physiological features. Even small alterations in neuron differentiation pathways can disrupt subsequent circuit organization, and catalyze the genesis of neurological disorders such as retardation syndromes, autism, and schizophrenia that cause exceptional individual suffering and have large social costs. However we still understand remarkably little about what happens in a newly formed neuron to select and guide neuron class-specific differentiation. To address this; our laboratory has focused on the following two fundamental questions:
Although a huge diversity of neuron classes is required for nervous system function, only a handful of signaling systems are used to generate this diversity. Signaling systems have extremely pleiotropic effects. Their final output is strongly dependent on the context in which they operate. The mechanisms that underlie this behavior are a key question in biology. Consequently we ask: How are outputs of the same signaling system altered in different neurogenetic contexts, thus leading to correct context-dependent initiation of class-specific differentiation programs?
Class-specific differentiation programs lead to distinct dendrite arbor morphologies and axonal projections, as well as particular sets of ion channels and transmitters. It is the combination of these features that creates the functional characteristics of any neuron class. This raises the question: How are neuron-differentiation processes translated into neuron class-specific morphologies and physiologies?
Yalgin C, Ebrahimi S, Delandre C, Yoong LF, Akimoto S, Tran H, Amikura R, Spokony R, Torben-Nielsen B, White KP, and Moore AW: "Centrosomin represses dendrite branching by orienting microtubule nucleation.", Nat Neurosci (2015)
Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, Samara C, Moore AW, Cho LT, Young GT, Weiss C, Schabhüttl M, Stucka R, Schmid AB, Parman Y, Graul-Neumann L, Heinritz W, Passarge E, Watson RM, Hertz JM, Moog U, Baumgartner M, Valente EM, Pereira D, Restrepo CM, Katona I, Dusl M, Stendel C, Wieland T, Stafford F, Reimann F, von Au K, Finke C, Willems PJ, Nahorski MS, Shaikh SS, Carvalho OP, Nicholas AK, Karbani G, McAleer MA, Cilio MR, McHugh JC, Murphy SM, Irvine AD, Jensen UB, Windhager R, Weis J, Bergmann C, Rautenstrauss B, Baets J, De Jonghe P, Reilly MM, Kropatsch R, Kurth I, Chrast R, Michiue T, Bennett DL, Woods CG, and Senderek J: "Transcriptional regulator PRDM12 is essential for human pain perception.", Nat Genet, 47(7), 803-808 (2015)
Taniguchi H, and Moore AW: "Chromatin regulators in neurodevelopment and disease: Analysis of fly neural circuits provides insights: Networks of chromatin regulators and transcription factors underlie Drosophila neurogenesis and cognitive defects in intellectual disability and neuro", Bioessays (2014)
Hohenauer T, and Moore AW: "The Prdm family: expanding roles in stem cells and development.", Development, 139(13), 2267-82 (2012)
Endo K, Karim MR, Taniguchi H, Krejci A, Kinameri E, Siebert M, Ito K, Bray SJ, and Moore AW: "Chromatin modification of Notch targets in olfactory receptor neuron diversification.", Nat Neurosci (2012)
Karim MR, and Moore AW: "Convergent local identity and topographic projection of sensory neurons.", J Neurosci, 31(47), 17017-27 (2011)
Kinameri E, Inoue T, Aruga J, Imayoshi I, Kageyama R, Shimogori T, and Moore AW: "Prdm proto-oncogene transcription factor family expression and interaction with the Notch-Hes pathway in mouse neurogenesis.", PLoS One, 3(12), e3859 (2008)
Jinushi-Nakao S, Arvind R, Amikura R, Kinameri E, Liu AW, and Moore AW.: "Knot/Collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape.", Neuron, 56(6), 963-78 (2007)