A central role for Islr2 (Linx) in direct pathway striatal projection neurons for the correct formation of the internal capsule and cerebral peduncle.

Authors

Saima Ali, Jacqueline M Ehrman, Paloma Merchan-Sala, J Matthew Kofron, Ronald R Waclaw, Kenneth Campbell

Published in

Developmental biology. Jul 04, 2026. Epub Jul 04, 2026.

Abstract

Islr2 (Linx) is a transmembrane protein that mediates correct formation of the internal capsule/cerebral peduncle. Here, we have utilized a combination of transgenic reporter alleles and immunohistochemical markers to trace striatal direct pathway (Sox8-EGFP), corticofugal (Fezf2-tdTomato), and thalamocortical (Netrin-G1) trajectories throughout development in several different permutations of Islr2 conditional knockout (cKO) mice. Firstly, we used Isl1^cre to recombine Islr2 in the newborn direct pathway striatal projection neurons (dSPNs) as well as the corridor (Co) cells and thalamic reticular nucleus (TRN) and found this resulted in a complete loss of the internal capsule/cerebral peduncle including dSPN, corticofugal and thalamocortical axons. Despite the severe dSPN axon defects in these cKOs, the Co forms correctly. To examine a potential role for Islr2 in the TRN, which borders the axonal trajectories of the rostral internal capsule, we used Foxd1^cre. These Islr2 cKOs showed no overt defects in dSPN, corticofugal or thalamocortical axons within the internal capsule/cerebral peduncle. Finally, to distinguish a role for Islr2 specifically in maturing SPNs versus newborn dSPNs and Co cells, we used Gpr88^cre and observed defasciculation and misrouting of dSPNs within the direct pathway. Importantly, these cKOs showed a notable reduction in corticofugal axons within the posterior internal capsule together with a loss of the cerebral peduncle while thalamocortical axons remained intact. Taken together, our results highlight a central role for Islr2 on dSPN axons for the correct assembly of the internal capsule/cerebral peduncle trajectories.

PMID:
42401396
Bibliographic data and abstract were imported from PubMed on 05 Jul 2026.

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