Institute of Child Health

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Dr Patrizia Ferretti

Development and Regeneration Group

Group Leader: Dr. Patrizia Ferretti

One major research interest concerns the origin of neural progenitors and the environmental conditions in which regeneration of the nervous system can takes place (e.g. role of certain growth factors such as members of the FGF family). A thorough understanding of the mechanisms underlying tissue and organ regeneration in the different models we are currently using my help to devise strategies for restoring functionality in damaged or diseased human tissues either by stimulating endogenous neural stem cells or by cell grafting approaches.

Another major theme is the skeletogenic differentiation of the neural crest in relation to normal and abnormal skull morphogenesis with a particular focus on the role of the transcription factor twist and of fibroblast growth factor receptors. Recent interests include the possibility of using osteoprogenitors from patients with craniosynostosis (bone biopsies provided by clinical colleagues at GOS) seeded on bioabsorbable scaffolds.

Overall, both the work on neural regeneration and on normal and abnormal craniofacial development / regeneration going on in the laboratory focus on the issues of cell plasticity and differentiation potential, and the role of FGF signaling in these processes.  A multidisciplinary approach and a broad range of cellular and molecular techniques are used to address these important issues.

Several current laboratory-based projects (e.g. molecular mechanisms underlying craniosynostosis and cranial bone repair) are closely integrated with the clinical research interests of  clinical and surgical colleagues at Great Ormond Street Hospital.

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Ongoing Projects

• Cellular and molecular basis underlying changes in regenerative capability in the developing spinal cord
• Role of peptidylarginine deiminases in neural progenitors in health and disease
• Establishment of 3D models for the study of human neural cells
• Adipose-tissue derived stem cells for craniofacial and neural repair
• Role of the choroid plexus in the developing brain
• Neural stem cell labelling and tracking with magnetic resonance imaging

Undifferentiated (left) and differentiating (right) human neurospheres

In vivo monitoring by MRI of NT2 neural stem cells labelled with ultrasmall superparamagnetic iron oxide (USPIO) particles (Sinerem) 14 days following stroke and cell injection (collaborative work between P. Ferretti and J. Sowden in the Developmental Biology Unit, M. Lythgoe and D. Gadian in the Radiology and Physics Unit  and J. Steinke at Imperial College, London)

Neurofilament-positive axonal swellings (arrowhead) are abundant in E15 damaged chick spinal cord but not in E11  cords (not shown).	Motor neurons retrogradely labelled from muscle (red) migrate into the regenerating spinal cord of tailed amphibians.

Expression of the transcri[ption factor Snail mRNA in fusing palatal shelves after 48 hours (hrs) in culture (t, tooth bud,; N, nasal side; O, oral side)