Poster Presentation ASSCR, AGCTS, ISCT ANZ and Friends Joint Scientific Conference 2019

Understanding the role of WNT signalling in generating midbrain dopaminergic neurons of the substantia nigra pars compacta /A9 subtype neurons (#221)

Shanti Sibuea 1 , Colin Prof. Pouton 1 , John Dr. Haynes 1
  1. Monash Institute of Pharmaceutical Science, Monash University, Melbourne, VICTORIA, Australia

Cell replacement therapy is one of the most promising strategies for the treatment of Parkinson’s disease (PD).  The degeneration of A9 sub-type midbrain dopaminergic (mDA) neurons leads to the movement disorders characteristic of PD.  Consequently, there has been considerable interest in the potential of hPSCs to provide a source of A9 neurons for transplantation.   Protocols for directed differentiation of hESCs into mDA neurons have been developed, based on knowledge of mouse brain development.  Several challenges remain, including the need to develop protocols that can enrich for A9 sub-type neurons, and the need to modulate the maturation of progenitors and survival of mature neurons.   Wnt signalling has been reported to influence mDA neuron specification and phenotype.  We studied the phenotype of cells during differentiation using a genetic reporter targeted downstream of the Lmx1a promoter in hESCs.  We exposed  our cultures to Wnt mimetics in the early (Day 3 -11)  and maturation stages (Day 40 – 65).  We observed that concentration-dependent activation of Wnt signalling altered the phenotype of mDA neurons both in early patterning and at the maturation stage.  This study provides insight into the development of appropriate cell therapies for PD.  

  • Have you presented your abstract at another international meeting?: No