BEGIN:VCALENDAR
PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20150120T154253Z
DTSTART:20150120T130000Z
DTEND:20150120T140000Z
SUMMARY:Heparanase 2 and LRIG2 direct functional differentiation of perip
 heral nerves
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}xuo-i4pjnk4
 o-xpiyu5
DESCRIPTION:Part of the Tissue Systems seminar series.                   
                                                                         
                                                   Growth factor signalli
 ng drives key steps in the motor neuron lineage. Critically\, what is po
 orly understood is how signalling is fine tuned to avoid over- or undera
 ctivity\, either of which could fatally compromise the generation of fun
 ctional neuro-muscular units. Our contention is that Hpse2\, an endogeno
 us inhibitor of the enzyme activity of classical heparanase\, and Lrig2\
 , a member of a family of plasma membrane proteins that control growth f
 actor signalling\, are key components of such a regulatory network. With
  colleagues in the Centre for Genomic Medicine\, we discovered that eith
 er HPSE2 or LRIG2 can be mutated in urofacial syndrome\, a congenital mo
 tor neuropathy. Applying these human discoveries to animal models provid
 es an excellent chance to increase our knowledge of how motor neurons no
 rmally develop and differentiate. With colleagues in the Faculty for Lif
 e Sciences\, we created the first vertebrate model of urofacial syndrome
  in Xenopus. Hpse2 knockdown caused skeletal muscle paralysis\, dysmorph
 ic motor nerves and deregulated growth factor signalling. Moreover\, Hps
 e2 and Lrig2 are normally detected in the ventrolateral domain of the ne
 ural tube\, in growth cones of neurites\, and in myotomes\, supporting r
 oles for the two proteins in neuron specification\, axon growth and syna
 ptogenesis\, respectively. Diseases affecting peripheral nerves affect 2
 % of the general population and produce unpleasant and crippling symptom
 s lasting for years. Curative treatments are urgently needed but are non
 -existent. Our ongoing studies to clarify processes underpinning normal 
 motor neuron development and differentiation will inform the future logi
 cal design of novel biological therapies for peripheral neuropathies (Da
 ly SB et al. Am J Hum Genet 11:963-9\, 2010\; Stuart HM\, Roberts NA et 
 al. J Am Soc Nephrol epub ahead of print PMID: 25145936\; Stuart HM et a
 l. Am J Hum Genet 92:259-64\, 2013\; Roberts NA et al. Hum Mol Genet 23:
 4302-14\, 2014)
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Lecture Theatre\, Michael Smith Building\, Manchester
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