The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.

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Background Eccrine spiradenocarcinoma (SC), also known as malignant eccrine spiradenoma, is a rare malignant cutaneous adnexal neoplasm arising from long-standing benign eccrine spiradenoma. Malignant skin tumors rarely show direct intracranial invasion. However, once the intracranial structure is infiltrated, curative excision with sufficient margins can become extremely difficult, particularly when the venous sinuses are involved. No effective adjuvant therapies have yet been established. Here, we report an extremely rare case of scalp eccrine SC with direct intracranial invasion, which does not appear to have been reported previously. Case presentation An 81-year-old woman presented with a large swelling on the parietal scalp 12 years after resection of spiradenoma from the same site. The tumor showed intracranial invasion with involvement of the superior sagittal sinus and repeated recurrences after four surgeries with preservation of the sinus. The histopathological diagnosis was eccrine SC. Adjuvant high-precision external beam radiotherapy (EBRT) proved effective after the third surgery, achieving remission of the residual tumor. The patient died 7 years after the first surgery for SC. Conclusions Scalp SC with direct intracranial invasion is extremely rare. Radical resection with tumor-free margins is the mainstay of treatment, but the involvement of venous sinuses makes this unfeasible. High-precision EBRT in combination with maximal resection preserving the venous sinuses could be a treatment option for local tumor control.

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