Research in this unit is concerned with the following areas of developmental biology:
- Development and regeneration of the nervous system
- Craniofacial development and repair
- Midline Defects (joint Neural Development Unit)
- Eye Diseases
- Orofacial development Group
Development and Regeneration Group
Group Leader: Dr. Patrizia Ferretti
The Ferretti’s laboratory has a long-standing interest in the basic mechanisms governing regeneration of a variety of complex body structures in vertebrates, and on the relationship between regeneration and the normal and abnormal development of such structures with a particular focus on the nervous system and craniofacial abnormalities. Within this context much work is focused on the issues of stem cell plasticity and differentiation potential and their underlying molecular basis, and on how this could be used to devise strategies for restoring functionality in damaged or diseased human tissues. A multidisciplinary approach and a broad range of cellular and molecular techniques are used to address these important issues.
Studies on spinal cord injury in a chick model have led to the discovery that inhibition of members of the PAD enzyme family reduce neural damage, and to subsequent development of a promising novel PAD inhibitor in collaboration with Prof. CM Marson that is currently being assessed in different models.
Much effort in the Ferretti’s laboratory is also devoted to the development of novel human 3-dimensional models relevant to tissue development and to modelling neural damage, including hypoxic-ischaemic damage, that could be used for studying disease mechanisms as well as fot toxicology studies and drug testing.
Furthermore, current laboratory-based projects aimed ad bioengineering craniofacial tissues using autologous stem cells (e.g. use of adipose tissue derived stem cells for cartilage repair) involve close collaborations with biomaterial scientists and are closely integrated with the clinical research interests of clinical and surgical colleagues at Great Ormond Street Hospital, UCL Ear Institute and the Royal Free Hospital.
Altogether, a central aim is to further develop both pharmacological and cell-based approaches to neuroprotection and craniofacial tissue repair building on an increasing understanding of basic cellular and molecular responses to environmental changes and disease.
- Role of peptidylarginine deiminases in health and disease
- Establishment of 3D models for the study of human neural cells
- Use of somatic stem cells including adipose-tissue and umbilical cord-derived stem cells for craniofacial and neural repair
- Cellular and molecular basis underlying changes in regenerative capability in the developing spinal cord
- Role of the choroid plexus in the developing brain
Undifferentiated (left) and differentiating (right) human neurospheres
Group Leader: Prof. Jane Sowden
in the eye development and repair group aims to identify the genetic
pathways underlying normal eye development and to understand how
mutations in key genes cause eye malformation and disease. Our research
is focussed on understanding the developmental regulation of ocular stem
and progenitor cells that offer the potential for repair and
regeneration of diseased eye tissue.
In the UK, 1 in every 1,000 children are visually impaired or blind. More than a quarter of all cases are caused by congenital eye defects. These include the condition microphthalmia, in which the embryonic eye fails to grow, conditions involving malformations of the anterior segment of the eye and glaucoma, and conditions involving abnormal development and degeneration of photoreceptor cells. Congenital eye defects are often found in association with other non ocular malformations and children with these syndromes are frequently seen by clinical colleagues at Great Ormond Street Hospital for Children NHS Trust.
Mutations in genes encoding transcription factors are the most common known cause of congenital eye defects. To improve understanding of the aetiology of these conditions, a range of experimental approaches (molecular biology, embryology, cell biology, genetics) are being used to explore the function and interactions between key transcription factors during eye development. The prevalence of different types of genetic change in affected individuals is being analysed to improve diagnosis and identify asssociated risk factors.
A central research theme is study of the molecular mechanisms regulating proliferation of retinal stem/progenitor cells and the generation of retinal neurons from these progenitor cells.
Research includes investigation of embryonic retinal progenitor cells and retinal stem/progenitor cells derived from the adult eye. We have recently shown that transplanted photoreceptor precursors can improve visual function in animal models of retinal disease. We are pursuing development of retinal stem therapy for the treatment of retinal disease in collaboration with Professor Robin Ali at
Adult-derived retinal stem cells are potentially useful as a source of new neurons for treatment of retinal disease. Identification of genetic pathways and environmental conditions that are sufficient to promote production of new retinal neurons from retinal stem cells is an important current goal.
- Retinal stem cells and their potential for treatment of retinal disease
- A study of microphthalmia and the role of the Chx10 gene in retinal progenitor cells
- Altered gene dosage as a mechanism for congenital eye defects and glaucoma
- Molecular genetic analysis of glaucoma and abnormal development of the anterior segment of the eye
- Analysis of the role of T-box genes in patterning and development of the retina and nervous system
Proliferation of retinal progenitor cells in the optic cup is reduced by
lack of the Chx10 transcription factor. Phosphohistone H3
immuno-labelling of mitotic retinal progenitor cells (green) at the
ventricular surface in the embryonic eye. +/+ is a normal eye and -/- is
a microphthalmic eye lacking Chx10.
Retinal stem cells isolated from the ciliary epithelium of the adult
ciliary body proliferate and form neurospheres in culture.
Immuno-labeled with the progenitor cell marker, nestin (green).
Molecular patterning across the dorso-ventral axis of the embryonic eye. Tbx5 gene expression (blue) is restricted to retinal progenitor cells in the dorsal peripheral region of the developing optic cup.
Transplanted photoreceptor precursor cells integrate and develop into mature photoreceptor cells (green) that form functional connections with the host retina (blue) and improve visual function [see MacLaren, Pearson et al Nature 2006; 44:203-7].
Transplanted cone photoreceptor (yellow) within the outer nuclear layer
(magenta) of a recipient retina [see Lakowski, Baron et al (2010) Hum. Mol.
- Analysis of craniofacial anomalies from a clinical, genetic and developmental point of view.
- Role of retinoid signalling in mouse palatogenesis.
Midline Defects Group
include study of the genetic pathways and underlying molecular events
that lead to common birth defects such as cleft palate, neural tube
defects and IUGR.
Eye Diseases and Glaucoma
Group Leader: Dr Kanwal Nischal
Page last modified on 26 jun 13 11:45