Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice
1 Department of Medicine, McMaster University, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada
2 Present address: Faculty of Applied Health Sciences, Brock University, 500 Glenridge Ave, St. Catharines, ON L2S 3A1, Canada
3 Present address: Biotechnology Group, Activation Laboratories, 1336 Sandhill Drive, Ancaster, ON L9G 4 V5, Canada
BMC Neuroscience 2013, 14:119 doi:10.1186/1471-2202-14-119Published: 11 October 2013
The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis.
Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture.
Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro.