02837nas a2200409   4500000000100000000000100001008004100002260001500043653002700058653001800085653002200103653002700125100001500152700001600167700003000183700002500213700002200238700002000260700002100280700001700301700001400318700001300332700001200345700002500357700001600382700002000398700001700418700001600435700001600451700001600467245006900483856005500552300001200607490000800619520178600627022001402413       2024                            d  c2024-02-2610aBiomedical Engineering10aEmbryogenesis10aNeural patterning10aPluripotent Stem Cells1 aXufeng Xue1 aYung Su Kim1 aAlfredo-Isaac Ponce-Arias1 aRichard O’Laughlin1 aRobin Zhexuan Yan1 aNorio Kobayashi1 aRami Yair Tshuva1 aYu-Hwai Tsai1 aShiyu Sun1 aYi Zheng1 aYue Liu1 aFrederick C. K. Wong1 aAzim Surani1 aJason R. Spence1 aHongjun Song1 aGuo-li Ming1 aOrly Reiner1 aJianping Fu00aA patterned human neural tube model using microfluidic gradients  uhttps://www.nature.com/articles/s41586-024-07204-7  a391-3990 v6283 aThe human nervous system is a highly complex but organized organ. The foundation of its complexity and organization is laid down during regional patterning of the neural tube, the embryonic precursor to the human nervous system. Historically, studies of neural tube patterning have relied on animal models to uncover underlying principles. Recently, models of neurodevelopment based on human pluripotent stem cells, including neural organoids1–5 and bioengineered neural tube development models6–10, have emerged. However, such models fail to recapitulate neural patterning along both rostral–caudal and dorsal–ventral axes in a three-dimensional tubular geometry, a hallmark of neural tube development. Here we report a human pluripotent stem cell-based, microfluidic neural tube-like structure, the development of which recapitulates several crucial aspects of neural patterning in brain and spinal cord regions and along rostral–caudal and dorsal–ventral axes. This structure was utilized for studying neuronal lineage development, which revealed pre-patterning of axial identities of neural crest progenitors and functional roles of neuromesodermal progenitors and the caudal gene CDX2 in spinal cord and trunk neural crest development. We further developed dorsal–ventral patterned microfluidic forebrain-like structures with spatially segregated dorsal and ventral regions and layered apicobasal cellular organizations that mimic development of the human forebrain pallium and subpallium, respectively. Together, these microfluidics-based neurodevelopment models provide three-dimensional lumenal tissue architectures with in vivo-like spatiotemporal cell differentiation and organization, which will facilitate the study of human neurodevelopment and disease.  a1476-4687