TY - JOUR AB - One of the earliest steps during the development of the nervous system is the establishment of neuronal polarity and the formation of an axon. The intrinsic mechanisms that promote axon formation have been extensively analyzed. However, much less is known about the extrinsic signals that initiate axon formation. One of the candidates for these signals is Insulin-like growth factor 1 (Igf1) that acts through the Igf1 (Igf1R) and insulin receptors (InsR). Since Igf1R and InsR may act redundantly we analyzed conditional cortex-specific knockout mice that are deficient for both Igf1r and Insr to determine if they regulate the development of the cortex and the formation of axons in vivo. Our results show that Igf1R/InsR function is required for the normal development of the embryonic hippocampus and cingulate cortex while the lateral cortex does not show apparent defects in the Igf1r;Insr knockout. In the cingulate cortex, the number of intermediate progenitors and deep layer neurons is reduced and the corpus callosum is absent at E17. However, cortical organization and axon formation are not impaired in knockout embryos. In culture, cortical and hippocampal neurons from Igf1r;Insr knockout embryos extend an axon but the length of this axon is severely reduced. Our results indicate that Igf1R/InsR function is required for brain development in a region-specific manner and promotes axon growth but is not essential for neuronal polarization and migration in the developing brain. AU - Jin, Jing AU - Ravindran, Priyadarshini AU - Di Meo, Danila AU - Püschel, Andreas W. DA - 2019-07-18 DO - 10.1371/journal.pone.0219362 LA - eng N1 - PLoS ONE 14 (2019) 7, e0219362, 1-20 N1 - This work was supported by the Deutsche Forschungsgemeinschaft (DFG) through a grant to A.W.P. (SFB 629, A15; SFB 1348, B03) and the Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM). N1 - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster). PY - 2019-07-18 TI - Igf1R/InsR function is required for axon extension and corpus callosum formation UR - https://nbn-resolving.org/urn:nbn:de:hbz:6-30189722613 Y2 - 2024-11-21T23:54:43 ER -