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Publication : Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling.

First Author  Alvarez S Year  2024
Journal  Cell Rep Volume  43
Issue  11 Pages  114954
PubMed ID  39547237 Mgi Jnum  J:358845
Mgi Id  MGI:7784912 Doi  10.1016/j.celrep.2024.114954
Citation  Alvarez S, et al. (2024) Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling. Cell Rep 43(11):114954
abstractText  We have identified an unexpected role for netrin1, a canonical axonal guidance cue, as a suppressor of bone morphogenetic protein (Bmp) signaling in the developing dorsal spinal cord. Using a combination of gain- and loss-of-function approaches in chicken and mouse embryonic models, as well as mouse embryonic stem cells (mESCs), we have observed that manipulating the level of netrin1 specifically alters the patterning of the Bmp-dependent dorsal interneurons (dIs), dI1-dI3. Altered netrin1 levels also change Bmp signaling activity, as assessed using bioinformatic approaches, as well as monitoring phosophoSmad1/5/8 activation, the canonical intermediate of Bmp signaling, and Id levels, a known Bmp target. Together, these studies support the hypothesis that netrin1 acts from the intermediate spinal cord to regionally confine Bmp signaling to the dorsal spinal cord. Thus, netrin1 has reiterative activities shaping dorsal spinal circuits, first by regulating cell fate decisions and then acting as a guidance cue to direct axon extension.
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