Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling
Year: 2024
Type: article
Abstract: We have identified an unexpected role for netrin1 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, embryonic stem cell (ESC), and mouse models, 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 measured by bioinformatics, and 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.
Source: Cell Reports
Authors: Sandy Alvarez, Sandeep Gupta, Yesica Mercado-Ayon, Kaitlyn Honeychurch, Cristian Rodriguez, Riki Kawaguchi, Samantha J. Butler
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: National Science Foundation, California Institute of Regenerative Medicine, National Institutes of Health, University of California, Los Angeles, California State University, Northridge, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1326384438, G205302978, G2923451624, G3277181742, Graduate Research Fellowship Program (GRFP), G5155488750, G5495043538, G5690963854, G6853726847, G6880221241, Research Tranining in Cellular and Molecular Biology, G7900453854, Investigating netrin1-mediated commissural axon guidance in the developing spinal cord, G9000002405, G9000039254, G9000100130, G9000184124, Assessing the mechanisms directing cell fate in the dorsal spinal cord
OpenAlex ID: W4404375237