Background: Transforming growth factor-beta 1 (TGF-β1) is a pleiotropic cytokine that regulates neurogenesis, migration, and synaptic plasticity during neural development. Coordinated expression of cell adhesion molecules (CAMs) is essential for these processes, yet the interplay between TGF-β1 signaling and specific CAMs—particularly E-cadherin, LICAM (L1 cell adhesion molecule), integrin β1, claudin-1, and VCAM-1 (vascular cell adhesion molecule-1)—remains incompletely defined in the developing nervous system. Objective: To characterize the activation dynamics of the TGF-β1 signaling pathway and determine the spatiotemporal expression and functional roles of E-cadherin, LICAM, integrin β1, claudin-1, and VCAM-1 during neural development. Methods: Neural tissue from embryonic and early postnatal rodent models was analyzed at key developmental stages (E10.5, E14.5, P0, P7). TGF-β1 pathway activation was assessed by phospho-Smad2/3 and PAI-1 expression. Expression and localization of the five adhesion molecules were evaluated using qRT-PCR, immunoblotting, immunofluorescence, and tissue clearing. Functional blocking experiments (neutralizing antibodies or siRNA) were performed in primary neural progenitor cell cultures and ex vivo slice cultures. Results: TGF-β1 pathway activation peaked during late embryogenesis (E14.5–E18.5), coinciding with robust upregulation of LICAM and integrin β1 in migrating neurons and axonal tracts. E-cadherin was transiently expressed in radial glia and neuroepithelial cells, declining sharply postnatally. Claudin-1 was restricted to blood–brain barrier-forming endothelial cells and tanycytes, while VCAM-1 was predominantly vascular but showed transient neuronal expression in the developing cortex. Functional blockade of integrin β1 or LICAM disrupted radial migration, whereas E-cadherin knockdown impaired neural progenitor aggregation. TGF-β1 stimulation upregulated LICAM and integrin β1 via Smad-dependent mechanisms; inhibition of TGF-β1 signaling reduced their expression and caused migration defects recapitulating the knockdown phenotypes. Claudin-1 and VCAM-1 were not directly regulated by TGF-β1 in neurons but responded in neurovascular niches. Conclusion: TGF-β1 pathway activation selectively drives expression of LICAM and integrin β1 during neural development, coordinating neuronal migration and axon guidance. E-cadherin supports early neuroepithelial integrity independent of TGF-β1, while claudin-1 and VCAM-1 primarily function in barrier and neurovascular interfaces. These findings establish a molecular axis linking TGF-β1 signaling to specific adhesion mechanisms essential for proper neural circuit formation.
