Lee HK , Lee HS , Moody SA .

NS23158 NINDS NIH HHS

Fig. 1. A schematic representation of main signaling pathways involved in NTFs development during embryogenesis. Five major signaling pathways including SHH, BMP, WNT, Notch ligands and FGF2, together crosstalk is represented. SHH ligand relieves the constitutive repression of the seven-pass receptor smoothened (SMO) by the modulation of the GLI transcriptional activators Gli1/2. Extracellular regulation of BMP signaling BMP induces the dimerization and then tetramerization of BMP receptors, leading to phosphorylation of the cytoplasmic signal transducer SMAD. WNT signaling activates β-catenin by modulating Frizzed and Dsh. Transcription factor LEF is required for enhancing of E2F1, consequently block Bmi1. The Notch and FGF2 signaling pathways have been implicated in regulating the neural differentiation and development. Notch interacts with NICD and mediates the effect of Hes1 and Gli/12. FGF2 activates JNK through binding with FGFR receptors, thus activating ATF2 regulatory mechanisms in neural development.

Fig. 2. A gene regulatory network of neural transcription factors that regulate the earliest steps in vertebrate neural development. Foxd4 is required for the expression of the remaining genes, and it directly activates Geminin, Zic2 and Sox11 (blue arrows). Together, these three genes mediate the downstream effects of Foxd4, which is to delay the expression of neural plate stem cell genes (Sox) and repress the expression of neural progenitor genes (Irx, Zic, bHLH).

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