I grew up in Madrid, Spain, and carried out my first degree in Biological Sciences at the Universidad Complutense in Madrid, graduating in 1986. I obtained my PhD (DPhil) from the University of Oxford (Madgalen College) in 1990, on Drosophila developmental genetics and supervised by Prof. Phil W. Ingham. I subsequently (1990-1992) obtained a post-doctoral fellowship from the Spanish Ministry of Science and Education to do a post-doctoral period with Prof Antonio García-Bellido, at the Universidad Autónoma de Madrid, working on the control of growth and form in Drosophila development.
I returned to UK with a Marie Curie Human Capital and Mobility Fellowship to do a second post-doc with Prof Andrea H. Brand at the Wellcome/CR-UK Institute, University of Cambridge (1993-1997). After this, I was awarded a Wellcome Trust Research Career Development Fellowship to establish my independent research group at the Department of Genetics, University of Cambridge (1997-2002). Here, I established my line of research into neuron-glia interactions during nervous system development. In 2001 I received an EMBO Young Investigator Award for my achievements as a young group leader.
In 2002, I moved to the School of Biosciences, University of Birmingham, appointed Senior Lecturer, and where I consolidated my research into nervous system development using Drosophila.
Research Theme within School of Biosciences: Molecular and Cell Biology
Lab website address: www.biosciences-labs.bham.ac.uk/hidalgo/
Nervous system development: structural and developmental plasticity
Our lab aims to understand how the nervous system is formed, and how it works. Structure and function come together in the course of development, and influence each other throughout life, endowing the nervous system with plasticity. As the animal grows and nervous system volume and cell number increase, the two cell types in the nervous system - neurons and glial cells - make adjustments that modify migration patterns, axonal trajectories, cell division and cell survival. These plastic adjustments result in the robust, reproducible formation of the nervous system across individuals, and over evolutionary time. Conversely, these cell interactions fail in diseases of the nervous system and brain (e.g. neurodegenerative diseases, psychiatric disorders and brain tumours) and upon injury (e.g. upon spinal cord injury and stroke).
We use the fruit-fly Drosophila because it is a very powerful model organism to address questions swiftly, in vivo and with single cell resolution. Our approach combines genetics, molecular biology, cell culture, computational analysis and in vivo confocal microscopy in fixed specimens and in time-lapse.
We collaborate with biochemists (Prof. N.J. Gay, Cambridge), electrophysiologists (Dr I. Robinson, Plymouth) and experts using mice and rats as model organisms (Prof. A. Logan, IBR Birmingham and Dr F. Matsuzaki, Riken, Japan).
We have recently discovered:
1. Drosophila Neurotrophins (DNTs):
That a neurotrophin protein family in Drosophila formed of DNT1, DNT2 and Spz regulate neuronal cell number, connectivity and synaptogenesis. This demonstrated conserved structure and function of the neurotrophin super-family from flies to humans. The findings support the notion that a common mechanism underlies the origin and function of all brains in evolution and that there are fundamental aspects in the way brain structure and function are linked, in fruit-flies and humans. These findings are important to use Drosophila as a model to understand the brain and to model brain diseases.
2. DNT receptors of the Toll superfamily
That the receptors for the DNTs belong to the Toll receptor super-family. Whereas Toll receptors have universal functions in innate immunity, we found that Toll-6 and Toll-7 in flies function as neurotrophin receptors to regulate neuronal number and targeting, and hebaviour. This reveals the distinct evolution of neurotrophin signalling, shared origins of the immune and nervous systems, and unforeseen relationships between the neurotrophin and Toll protein superfamilies.
3. A gene network for CNS repair in Drosophila.
We have a discovered a gene network that can promote injury repair in the CNS of Drosophila. We have established a novel paradigm to investigate central nervous system regeneration and repair in fruit-flies. We have shown that we can manipulate this gene network to prevent or promote injury repair. We are collaborating with mammalian experts to directly test whether this gene network also operates in mammalian glia using mice - closer to human conditions.
4. Research in Imaging.
To address questions on structural plasticity, it is essential to acquire quantitative information on cell number (e.g. the number of dying or dividing cells, neurons or glia, in different genotypes or conditions) and number of synapses. Thus we developed programmes to enable us to do exactly that, for the whole central nervous system of Drosophila embryos, larvae and the adult brain. We also developed a programme to track crawling larvae. All of our programmes were developed as ImageJ plug-ins and are freely available through our lab web-page.
Research by the Hidalgo group is funded by: The Wellcome Trust, BBRSC project grants and EU Marie Curie IntraEuropean and International Incoming Fellowship and The Royal Society, and in the past has also received funding from the MRC and EMBO and PhD studentships from the BBSRC, MRC and the Government of Brunei.
Sutcliffe B, Forero MG, Zhu B, Robinson I and Hidalgo A (2013) Neuron-type specific functions of DNT1, DNT2 and Spz at the Drosophila neuromuscular junction. PLoS One, 2013 Oct 4;8(10):e75902. doi: 10.1371/journal.pone.0075902
McIlroy G, Foldi I, Aurikko J, Wentzell JS, Lim MA, Fenton JC, Gay NJ and Hidalgo A (2013) Toll-6 and Toll-7 function as neurotorphin receptors in the Drosophila melanogaster CNS. Nature Neuroscience 16, 1248-1256. doi: 10.1038/nn.3474. Recommended by Faculty of 1000 http://f1000.com/prime/718049779?bd=1&ui=21597
Kato, K., Hidalgo, A. An Injury Paradigm to Investigate Central Nervous System Repair in Drosophila.(2013) J. Vis. Exp. (73), e50306, doi:10.3791/50306. http://www.jove.com/video/50306/an-injury-paradigm-to-investigate-central-nervous-system-repair
Forero, Kato and Hidalgo (2012) Automatic cell counting in vivo in the larval nervous system of Drosophila. J Microscopy. 2012 May;246(2):202-12. doi: 10.1111/j.1365-2818.2012.03608
Kato K, Forero MG, Fenton JC and Hidalgo A (2011) The glial regenerative response to central nervous system injury is enabled by Pros-Notch and Pros-NFkB feedback. PLoS Biology 9: e1001133
Forero MG and Hidalgo A (2011) Image processing methods for automatic cell counting in vivo or in situ using 3D confocal microscopy. In "Advanced Biomedical Engineering: Ed. Gargiulo GD and McEwan A. Intech Open Access pages 183-204.
Hidalgo, Kato, Sutcliffe, McIlroy, Bishop and AlAhmed (2010) Trophic neuron-glia interactions and cell number adjustments in the fruit-fly. Glia DOI: 10.1002/glia.21092.
Forero, Learte, Cartwright and Hidalgo (2010) DeadEasy MitoGlia: automatic counting of mitotic cells and glia in the central nervous system of Drosophila. PLoS One 5, e10557
Forero, Pennack, and Hidalgo (2010) DeadEasy neurons: Automatic counting of HB9 neuronal nuclei in Drosophila. Cytometry Part A 77A, 371-378
Forero, Pennack, Learte and Hidalgo (2009) DeadEasy caspase: automatic counting of apoptotic cells in Drosophila. PLoS One 4, e5441.
Zhu, Pennack, McQuilton, Forero, Mizuguchi, Gu, Fenton and Hidalgo (2008) Drosophila neurotrophins reveal a common mechanism of nervous system formation. PLoS Biology 6, e284. See also pubcast at: www.scivee.com/node/8389 Recommended by Faculty of 1000: http://f1000.com/prime/1158489
Learte, Forero and Hidalgo (2008) Gliatrophic and gliatropic functions of PVR signalling during axon guidance. Glia 56, 164-176
Griffiths, Benito-Sipos, Fenton, Torroja and Hidalgo (2007) Two distinct mechanisms segregate Prospero in the longitudinal glia underlying the timing of interactions with axons. Neuron-Glia Biology, 3, 75-88
Hidalgo, Learte, McQuilton, Pennack and Zhu (2006) Gliatrophic and neurotrophic contexts in Drosophila. Brain, Behaviour and Evolution 68, 173-180
Griffiths & Hidalgo (2004) Prospero maintains the proliferative potential of glial precursor cells enabling them to respond to neurons in the CNS. The EMBO J 23, 2440-2450
Kinrade & Hidalgo (2004) Local neuron-glia interactions change the response of axons to the Robo code. Neuron Glia Biology 1, 101-112.
Hidalgo & Griffiths (2004) Coupling glial numbers to axonal patterns. Cell Cycle 3, 1118-1120.
Hidalgo (2002) Interactive nervous system development: control of cell survival in Drosophila. Trends in Neurosciences 25, 365-370
Hidalgo, Kinrade, and Georgiou (2001) The Drosophila neuregulin Vein maintains glial survival during axon guidance in the CNS. Developmental Cell 1, 679-690