Non-canonical Wnt Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons
Melissa G McKenzie, Lucy Cobbs, Patrick D Dummer, Timothy J Petros, Michael M Halford, Steven A Stacker, Yimin Zou, Gord J Fishell, Edmund Au
Neuron | CELL PRESS | Published : 2019
GABAergic interneurons have many important functions in cortical circuitry, a reflection of their cell diversity. The developmental origins of this diversity are poorly understood. Here, we identify rostral-caudal regionality in Wnt exposure within the interneuron progenitor zone delineating the specification of the two main interneuron subclasses. Caudally situated medial ganglionic eminence (MGE) progenitors receive high levels of Wnt signaling and give rise to somatostatin (SST)-expressing cortical interneurons. By contrast, parvalbumin (PV)-expressing basket cells originate mostly from the rostral MGE, where Wnt signaling is attenuated. Interestingly, rather than canonical signaling thro..View full abstract
Awarded by NIH
The authors wish to thank Kat Hadjantonakis and Wange Lu for generous donation of Tcf/Lef: H2B-dGFP and Ryk<SUP>-/-</SUP> animals, respectively; Andre Goffinet for guidance on Vangl2 mutants; Dhananjay Bambah-Mukku and Marian Fernandez Otero of the Dulac and Fishell laboratories, respectively, for RNA-scope protocol advice and reagents; and Zhimin Lao and Alexandra Joyner for helpful discussions about Shh signaling and performing Gli1 in situ hybridization. This work was supported by the following NIH grants: F30 MH087045 (M.G.M.), T32 MH015174-40 (M.G.M.), R01-NS081297 (G.J.F.), R01-MH071679 (G.J.F.), P01-NS074972 (G.J.F.), as well as generous support from the Simons Foundation (G.J.F.) and the Whitehall Foundation (E.A.). M.G.M. was supported by the NYU Medical Scientist Training Program.