|R e s e a r c h I n t e r e s t s|
|Neuronal specification during nervous system development and maturation in Drosophila
Complex nervous system function depends upon the generation of many different subtypes of neurons and the lifelong modulation of their function by intercellular communication. The identity and function of a particular neuronal subtype is a product of the unique repertoire of ‘terminal differentiation’ genes that it expresses (eg. guidance molecules, ion channels, receptors, neurotransmitter biosynthetic enzymes, neuropeptides etc).These genes are turned on after the neuron is born, but how neurons turn on the right set of genes is still poorly understood. Two regulatory inputs have been shown to play a role in regulating the expression of such ‘terminal differentiation’ genes; 1) the unique code of transcription factors expressed within the neuron, and 2) factors/signals that are secreted from the target cell that the neuron innervates. Our studies in Drosophila have demonstrated that these two inputs may actually functionally intersect to determine the mature gene expression repertoire of neurons.Our research aims to investigate the mechanisms by which neurons selectively express the genes that define their unique identities and functions, exploring the roles of combinations of transcription factors and extrinsic signals. The genes and mechanisms that govern cell specification are highly conserved from invertebrates to humans. Therefore, we can learn much about the fundamental principles and molecular mechanisms relevant to vertebrate neuronal differentiation using the simpler nervous system and genetic amenability of Drosophila.Disruption of transcription factors has been linked to congenital neurological disorders, and disruption of intercellular communication and trafficking of target-derived signals has been implicated in neurodegenerative disorders. Our studies will provide a mechanistic understanding of how these factors control gene expression pertinent to neuronal function, advancing our understanding of the aetiology of neurological disorders.Resources
Our laboratory is situated in the Life Sciences Institute on the UBC Main Campus. Together with Dr. Shernaz Bamji, we run The Facility for Synaptic Imaging which consists of upright and inverted Olympus FV1000 laser scanning confocal microscopes. We also share a dedicated, fully-equipped Drosophila Facility with other fly labs in the building.
|S e l e c t e d P u b l i c a t i o n s|
Allan DW and Thor S (2015) Transcriptional Selectors, Masters and Combinatorial Codes: Regulatory Principles of Neural Subtype Specification. WIREs Developmental Biology. Wiley Interdiscip Rev Dev Biol. 2015 Apr 8.
Kerr C, Wang Q, Keatings K, Khong A, Allan DW, Yip C, Foster L, and Jan E. (2015) The 5’untranslated region of a novel infectious molecular clone of the dicistrovirus Cricket paralysis virus modulates infection. Journal of Virology. March: 463-15.
Zheng C, Tham CTT, Keatings K, Fan S, Liou AYC , Numata Y, Allan DW and Numata M (2014) Secretory Carrier Membrane Protein (SCAMP) Deficiency Influences Behavior of Adult Flies Front. Cell Dev. Biol. doi: 10.3389/fcell.2014.00064
Garaulet DL, Castellanos MC, Bejarano F, Sanfilippo P, Tyler DM, Allan DW, Sánchez-Herrero E, Lai EC. (2014) Homeotic function of Drosophila Bithorax-complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the CNS. Developmental Cell. 29(6):635-48
Castellanos M, Tang CYJ, Allan DW. Female-biased dimorphism underlies a female-specific role for post-embryonic Ilp7-neurons in Drosophila fertility. Development. 140: 3915-3926.
Veverytsa L, Allan DW (2013) Subtype specific neuronal remodeling during Drosophila metamorphosis. Invited Review. Fly. 7(2):78-86
Szabat M, Kieffer TJ, Hoffman BG, Lynn F, Allan DW, Johnson JD (2012) b-Cell maturity and plasticity: Developmental biology meets physiology in the adult pancreas. Diabetes 61: 1365-1371
Veverytsa L and Allan DW (2012) Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in Drosophila. Proceedings of the National Academy of Sciences of USA (PNAS) 109 (13): E748–E756
Eade KT, Fancher HA, Ridyard MS, Allan DW (2012) Developmental transcriptional networks are required to maintain neuronal subtype identity in the mature nervous system. PLoS Genetics 8(2): e1002501
Veverytsa, L and Allan DW (2011) Retrograde BMP-signaling controls Drosophila behavior through regulation of a peptide hormone battery. Development. 138(15):3147-5
Cowan CM, Sealey MA, Quraishe S, Targett M-T, Marcellus K, Allan DW and Mudher A (2011). Review. Modelling Tauopathies in Drosophila: insights from the fruit fly. International Journal of Alzheimer’s Disease 2011: 598157 (16 pages).
Eade KT and Allan DW (2009) Neuronal phenotype in the mature nervous system is maintained by target-derived BMP signaling. Journal of Neuroscience 29: 3852-3864.
Allan DW (2008) Review. Combinatorial Codes in Neuronal Specification. The Encyclopedia of Neuroscience. Springer Press. Binder, M.D.; Hirokawa, N.; Windhorst, U.; Hirsch, M.C. (Eds.).
Allan DW, Park D, St. Pierre SE, Taghert PH, Thor S (2005) Regulators acting independently and in combinatorial codes to specify different aspects of neuronal identity. Neuron 45: 689-700.
Miguel-Aliaga I, Allan DW, Thor S (2004) Independent roles of the dachshund and eyes absent genes in the specification of neuropeptidergic cell identity. Development 131(23): 5837-5848.
Allan DW, Pierre SE, Miguel-Aliaga I, Thor S (2003) Specification of neuropeptide cell identity by the integration of retrograde BMP signaling and a combinatorial transcription factor code. Cell 113(1): 73-86.
Allan DW and Thor S (2003) Preview. Together at last. bHLH and LIM-HD regulators cooperate to specify motor neurons. Neuron 38(5): 675-7.
Further publications can be found here.