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We now demonstrate that proteins regulating polarity in other cells including partitioning defective 3 (PAR3), PAR6, protein kinase C\u03b6 (PKC\u03b6), and glycogen synthase kinase 3\u03b2 (GSK3\u03b2) are expressed in developing enteric neurons with a polarized distribution. Blocking PKC\u03b6 or GSK3\u03b2 reduces ENS precursor migration and induces the formation of multi-axonal neurons. Axon elongation also depends on SMURF1 (SMAD specific E3 ubiquitin protein ligase 1), which promotes RhoA degradation and associates with polarity proteins. SMURF1 inhibition, however, does not increase the number of multi-axonal neurons in ENS precursors. These data link cell surface Ret activation with molecular machinery controlling cytoskeletal dynamics and suggest that polymorphisms influencing PKC\u03b6 or GSK3\u03b2 might alter Hirschsprung disease penetrance or expressivity by affecting ENS precursor migration.<\/jats:p>","DOI":"10.1523\/jneurosci.0870-07.2007","type":"journal-article","created":{"date-parts":[[2007,8,29]],"date-time":"2007-08-29T16:24:00Z","timestamp":1188404640000},"page":"9458-9468","source":"Crossref","is-referenced-by-count":35,"title":["Protein Kinase C\u03b6 and Glycogen Synthase Kinase-3\u03b2 Control Neuronal Polarity in Developing Rodent Enteric Neurons, whereas SMAD Specific E3 Ubiquitin Protein Ligase 1 Promotes Neurite Growth But Does Not Influence Polarity"],"prefix":"10.1523","volume":"27","author":[{"given":"Bhupinder P. 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