| First Author | Usardi A | Year | 2017 |
| Journal | Dev Neurobiol | Volume | 77 |
| Issue | 1 | Pages | 75-92 |
| PubMed ID | 27328461 | Mgi Jnum | J:336794 |
| Mgi Id | MGI:7414150 | Doi | 10.1002/dneu.22412 |
| Citation | Usardi A, et al. (2017) The immunoglobulin-like superfamily member IGSF3 is a developmentally regulated protein that controls neuronal morphogenesis. Dev Neurobiol 77(1):75-92 |
| abstractText | The establishment of a functional brain depends on the fine regulation and coordination of many processes, including neurogenesis, differentiation, dendritogenesis, axonogenesis, and synaptogenesis. Proteins of the immunoglobulin-like superfamily (IGSF) are major regulators during this sequence of events. Different members of this class of proteins play nonoverlapping functions at specific developmental time-points, as shown in particular by studies of the cerebellum. We have identified a member of the little studied EWI subfamily of IGSF, the protein IGSF3, as a membrane protein expressed in a neuron specific- and time-dependent manner during brain development. In the cerebellum, it is transiently found in membranes of differentiating granule cells, and is particularly concentrated at axon terminals. There it co-localizes with other IGSF proteins with well-known functions in cerebellar development: TAG-1 and L1. Functional analysis shows that IGSF3 controls the differentiation of granule cells, more precisely axonal growth and branching. Biochemical experiments demonstrate that, in the developing brain, IGSF3 is in a complex with the tetraspanin TSPAN7, a membrane protein mutated in several forms of X-linked intellectual disabilities. In cerebellar granule cells, TSPAN7 promotes axonal branching and the size of TSPAN7 clusters is increased by downregulation of IGSF3. Thus IGSF3 is a novel regulator of neuronal morphogenesis that might function through interactions with multiple partners including the tetraspanin TSPAN7. This developmentally regulated protein might thus be at the center of a new signaling pathway controlling brain development. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 75-92, 2017. |
