{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNEURL1B belongs to the neuralized family of E3 ubiquitin ligases that modulate Delta–Notch signaling by regulating the stability and activity of Notch ligands. In mammals, neuralized proteins (including NEURL1B homologs) interact directly with ligands such as Delta‐like and Jagged family members, thereby influencing ligand endocytosis and signal propagation during early brain development. This regulation is critical for the precise temporal and spatial control of cell–cell communication that underlies neuronal specification and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlthough many of the provided studies focus on members of the basic helix–loop–helix transcription factor family (for example, NeuroD and Math proteins) that dictate cell fate, neurite outgrowth, axon targeting, and synaptic connectivity in diverse neuronal populations"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "12"}]}, {"type": "t", "text": ", these studies provide an important contextual framework. In particular, the dynamic transcriptional programs they describe during neuronal maturation and circuit formation put into perspective the potential interplay between NEURL1B‐mediated Notch modulation and the activity of neuronal fate determinants. NEURL1B could act in parallel or in crosstalk with the NeuroD/Math pathways, thereby contributing indirectly to processes such as progenitor maintenance, neuronal differentiation, neuritogenesis, and connectivity refinement."}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTaken together, insights from these diverse studies suggest that while neuralized proteins like NEURL1B directly regulate Notch ligand turnover and signaling—thereby impacting neurodevelopment—the broader orchestration of neuronal fate, connectivity, and survival also depends on a network of transcription factors. NEURL1B’s modulation of Notch signaling establishes one facet of a multi‐layered regulatory system, where balanced ubiquitination of ligands collaborates with bHLH‐driven transcription to fine‐tune the differentiation and functional integration of neurons. Further exploration of NEURL1B’s specific roles within this framework could illuminate its contribution to neurodevelopmental processes and disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Grete Rullinkov, Richard Tamme, Anzelika Sarapuu, et al. 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