SupplementarySectionOne-Springer.docVIP

Description of literature based gene regulatory network Ngn1 and Ngn2 are required to specify early-born glutamatergic neurons (those expressing markers such as VGLUT2/Slc17a6) that populate Layers V-VI of the developing neocortex and specifically express Robo1, Etv1, and Tbr1 1. Otx1 is also a marker for deep layer neurons in the developing dorsal telencephalon, however, it is also expressed in progenitor cells 2. Based in part on evidence in cranial ganglia, Ngn1 and Ngn2 positively regulate Neurod2, Neurod and Nscl1 3,4. Ngn2 is activated by the Wnt pathway in dorsal forebrain5,6, and can subsequently repress subcortical GABAergic neuronal phenotypes through inhibition of Mash1 1. Pax6 activates Ngn2 and Ngn17,8, while Ngn2 may cooperate with Pax6 to regulate Ngn1 in the developing dorsal forebrain 9. Ngns are thought to activate the glutamatergic phenotype through activation of an intermediate set of bHLH neural differentiation transcription factors, including Neurod, Neurod6 and Neurod2 10,11 and the homeobox transcription factor Eomes /Tbr2, which in turn may regulate Tbr1, based on sequential expression patterns12. Id2 is a cortical neuronal marker that may be regulated by Ngn2, most likely via downstream bHLH transcription factors, such as the Neurods1,13. Pax6 expression is necessary for the differentiation of late-generated neurons that populate Layers II-IV and express Satb2 and Pou6f1/Oct614,15. Mash1 initiates specification and differentiation of inhibitory neurons in the ventral telencephalon through activation of the homeobox transcription factors Dlx1 and Dlx2, which in turn activate Dlx516. Dlx1 and Dlx2 are thought to play a role in the activation of Arx, an important determinant of GABAergic cell fate17. Predicted downstream targets of the Dlxs include Gad1, Gad2, Slc6a1/GABA-T1, Slc32a1(GABA/glyT)1. The neural progenitor population within both the dorsal and ventral forebrain during this period of neurogenesis express high levels of bH