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Background/Objectives The complexity of cranio-facial development, particularly suture closure, allows for many complex anomalies of the face (clefts) and brain (encephaloceles).Cranial nerves and vessels, access the skull through foramina – at suture edges and through bones.Major failure of adequate suture closure results in clefts: minor breaches, in encephalocelesRecent progress highlight mechanisms of suture development at points of access to intra-cranial spaces.Methods Review of apt neurodevelopmental and neuropathological literature.Results Neurodevelopmentally, Neural Crest (NC) cells delaminate from neural tube on Gestation Day 21.Interactions between NC and the neural tube derivatives continue throughout development and life.The formation of meninges, underlying cortex, cranial nerves, vessels of face and brain, facial and skull bones, spinal-autonomic-peripheral nerves – rely on NC functions.NC-neural tube functional interactions are both time- and space-dependent.Vessels and nerves that traverse the skull inhibit apposition of endocranial sutures at those points.Emissary veins, connecting diploic veins, intra-cranial venous sinuses and scalp veins, remain understudied.Conclusion Many congenital structural abnormalities of skull, associated vessels, and even brain, have their origin – and can be explained by – aberrant interactions between neural crest and neural tube derivatives.Future research – in areas as disparate as migraine and neurodegeneration – await clarification of the role of extra- to intra-cranial connections that allow for the external environment’s temperature and pressure inputs into the brain compartments.