Research group of Dr. Alicia Hidalgo

Research group of Dr. Alicia Hidalgo

The Hidalgo lab (left to right): Kentaro Kato, Ben Sutcliffe, Graham McIlroy, Alicia Hidalgo and Manuel Forero.

Dr. Alicia Hidalgo is a senior lecturer and research group leader in the School of Biosciences at the University of Birmingham. The Hidalgo lab is interested in the genetic, cellular and molecular mechanisms that underlie the formation of the nervous system, in particular its developmental plasticity, such as the adjustments that neurons and glial cells make as an animal grows and its nervous system develops. This research is a pre-requisite to understanding nervous system function, brain evolution, the mechanisms underlying brain diseases such as neurodegeneration, psychiatric disorders and brain tumors, and for gaining new insights into how to repair the injured nervous system.

Born in Madrid, Alicia studied for a BSc at the Complutense University of Madrid before obtaining a PhD in Developmental Biology from the University of Oxford. She has held postdoctoral positions at the Autonomous University of Madrid and the University of Cambridge. In 1997, Alicia was appointed as a Wellcome Trust Research Career Development Fellow within the Department of Genetics at the University of Cambridge. She moved to her current position at the University of Birmingham in 2002. Alicia has won a number of awards, including the EMBO Young Investigator Award in 2001.

Allan Williams

Rachel Griffiths, who completed her PhD with Alicia Hidalgo and who created the images shown in figures 1 and 2.

Researchers in the Hidalgo lab focus their research on the developmental plasticity of the nervous system into two broad areas, neurotrophins and glial cells.

In vertebrates, neurotrophins control neuronal survival, axon guidance, connectivity, circuit formation, synaptic plasticity, synaptic transmission, learning and memory. They are the key to the brain’s function. The Hidalgo lab has identified a neurotrophin family in Drosophila that is involved in the control of neuronal survival and targeting. This supports the notion that there is a common evolutionary mechanism, shared amongst all animals, that underlies the origin of the brain. The lab aims to determine the molecular mechanisms by which Drosophila neurotrophins enable neurons to establish functional circuits as the nervous system grows. They are also interested in how the structure and function of the nervous system arose during evolution and what happens when neurotrophin function is altered (e.g. neurodegenerative diseases, such as Alzheimer’s, and psychiatric diseases).

Neurons interact closely with glial cells during the formation of axonal networks. These interactions maintain neuronal and glial cell survival and glial cell division. This is crucial for the timely delivery of discrete numbers of glial cells which enables axon guidance, axonal sorting through time and axonal enwrapment. The molecular and cellular mechanisms that bring axonal networks together with the timely and ordered adjustment of glial cell populations during growth are unclear. Alicia and her colleagues are therefore interested in understanding the molecular mechanisms underlying the control of glial cell numbers in relation to axons. This is important for understanding the origin of gliomas (the most common cause of brain tumors) and demyleinating diseases such as multiple sclerosis, and for further understanding of how to repair nervous system injury, such as damage to the spinal cord.

The Hidalgo lab uses Drosophila as a model organism because it is a powerful organism to uncover gene networks and analyze gene function in vivo and with single cell resolution. Drosophila is already successfully used by many labs to model human brain and nervous system diseases. Alicia’s lab uses genetic and molecular biology techniques, computational analysis and in vivo confocal microscopy of fixed specimens and in time-lapse.

Alicia says ‘We use Volocity for 3D rendering, and for cross sectional views. We have used Volocity’s 3D rendering a lot to visualize clusters of cells stained with two or three markers, and to count them. Volocity is very useful because we can visualize the nuclei as solid spheres and the cytoplasm as transparent and we can interactively rotate the clusters in many directions: altogether, this makes the identification of each cell in the clusters very accurate. This was crucial for our glial proliferation studies’.

 

GFP-actin

Figure 1: This figure shows a cross section of the embryonic ventral nerve cord of Drosophila, stained for nuclei with TOTO3 (blue), for glial cells with anti-β-gal antibodies that detect β-galactosidase produced by a Longitudinal Glia-LacZ reporter (green) and for neurons and neuroblasts with anti-Prospero (red). Glial cells can be seen to enwrap the axonal cables (neuropile) which appear unstained in black.

 

GFP-actin

Figure 2: This figure shows longitudinal glia expressing the gene prospero as they divide. The longitudinal glia of the Drosophila embryonic ventral nerve cord of the CNS are visualized here with anti-β-gal for a Longitudinal Glia-LacZ reporter (green), mitosis with anti-phospho-Histone H3 (red) and anti-Prospero (blue), rendered in Volocity.

Prospero positive glia divide, and some of them only switch off prospero after division. The gene prospero plays an important role in linking glial proliferation and axon guidance. The Hidalgo lab used Volocity to visualize and count the glial cells.                  

 

To find out more about research in the Hidalgo lab, please visit:
http://www.biosciences.bham.ac.uk/labs/hidalgo/index.htm