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bioRxiv · 10.64898/2026.03.05.709688

A tunnel microtract organ for T cell progenitor homing is formed by neural crest morphogenesis via Sox10-Cdc42 axis

Li, L.·Zhao, F.·He, J.·Xiao, L.·Chen, H.·Li, Z.·Lu, Y.·Duan, L.·Zhao, J.·Chen, G.·Huang, X.·Luo, L.
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Abstract

Thymic colonization by T cell progenitors (TCPs) is essential for adaptive immunity, yet the guiding tissues remain elusive. Here, we unveiled a tunnel microtract (TMT) as an organ indispensable in TCPs homing in both zebrafish and mouse. Disruption of TMT leads to compromised T cell development. Specifically, the zebrafish TMT were positioned bilaterally beneath the fifth branchial levator muscle, connecting the thymus and kidney. They are semi-coiled, non-vascular, non-lymphatic tubes of epithelial signatures. Impressively, Sox10 activates Cdc42 to promote F-actin remodeling in neural crest cells (NCCs), leading to precise elongation and tight packaging of a low-permeability TMT. Remarkably, a homologous CD34 TMT was observed in mice, which bilaterally enveloped the embryonic thymus and extended into the thyroid cartilage. Sox10-Cdc42 signalling functioned recapitulatively in NCC morphogenesis during its construction. These findings establish TMT as an unappreciated NCC-derived organ in TCPs homing, with implications in T cell development and immune disorders.

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Li, L., Zhao, F., He, J., Xiao, L., Chen, H., Li, Z., Lu, Y., Duan, L., Zhao, J., Chen, G., Huang, X., Luo, L.. 2026-03-07. A tunnel microtract organ for T cell progenitor homing is formed by neural crest morphogenesis via Sox10-Cdc42 axis. https://doi.org/10.64898/2026.03.05.709688

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