Asymmetric activation of Dll4-Notch signaling by Foxn4 and proneural factors activates BMP/TGFβ signaling to specify V2b interneurons in the spinal cord

• DOI: 10.1242/dev.092536
• Publication Date: 2013-11-21T02:44:48Z
• Authors: Kamana Misra; Huijun Luo; Shengguo Li; Michael Matise; Mengqing Xiang
• Keywords: Hes3 signaling axis

During development of the ventral spinal cord, V2 interneurons emerge from p2 progenitors and diversify into two major subtypes, V2a V2b, that play key roles in locomotor coordination. Dll4-mediated Notch activation a subset precursors constitutes crucial first step towards generating neuronal diversity this domain. The mechanism behind asymmetric downstream signaling events are, however, unknown at present. We show here Ascl1 Neurog basic helix-loop-helix (bHLH) proneural factors are expressed mosaic pattern Foxn4 is required for setting maintaining expression mosaic. By binding directly to conserved Dll4 enhancer, activate expression, whereas proteins prevent effect, thereby resulting expressing different combinations transcription factors. Lineage tracing using Cre-LoxP system reveals selective precursors, initially excluded V2b precursors. provide evidence BMP/TGFβ activated responsible activation. Using gain-of-function approach by inhibiting signal transduction with pathway antagonists RNAi knockdown, we further demonstrate both necessary sufficient fate specification. Our data together thus suggest may serve as trigger initiate Dll4-Notch subsequent