---
title: "Timed binary WNT activity models the early human neural axis — preprint report"
id: "biorxiv-12-timed-binary-wnt-activity-is-sufficient-to-model-the-early-human-neural-axis"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-12-timed-binary-wnt-activity-is-sufficient-to-model-the-early-human-neural-axis"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.17.759682v1?rss=1"
published_at: "2026-10-20T11:07:14.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Timed binary WNT activity models the early human neural axis — preprint report
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-12-timed-binary-wnt-activity-is-sufficient-to-model-the-early-human-neural-axis
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.17.759682v1?rss=1)
- **Published At:** 2026-10-20T11:07:14.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The preprint reports that controlled, time-limited binary **WNT** signalling is sufficient to reproduce features of the early human neural axis in an experimental system. - Authors are led by James O.S. Hackland and include a multi-institutional team; many contributors are affiliated with Memorial Sloan Kettering Cancer Center and other institutions. - The manuscript is a preprint on bioRxiv and has not been peer reviewed; the DOI is provided on the source page. - The source text does not supply experimental parameters such as dosing, timing windows, cell types used, organoid or monolayer format, or culture conditions; those methodological details were not reported in the accessible source excerpt. - Primary endpoints, quantitative outcomes, sample sizes, and statistical analyses are not described in the available source content; the study team did not report these elements in the excerpt. - The preprint claims sufficiency of timed binary **WNT** activity to model early neural patterning, but the source text does not include validation assays, marker analyses, or comparative benchmarks. - Open questions remain (based on the source): reproducibility across cell lines, exact temporal control mechanisms, scalability of the model, and how closely the model maps to in vivo human embryonic stages. - Readers should interpret findings as preliminary until peer review and until the full methods, datasets, and analyses are publicly available.
## Clinical Analysis & Structured Key Points
Timed binary WNT activity is sufficient to model the early human neural axis | bioRxiv Skip to main content New Results Timed binary WNT activity is sufficient to model the early human neural axis View ORCID Profile James O.S. Hackland , View ORCID Profile Giridhar Anand , View ORCID Profile Ragavi Vijayakumar , View ORCID Profile Xiaoyi Wang , View ORCID Profile Vittoria Dickinson Bocchi , View ORCID Profile Eve S Rowland , View ORCID Profile Donghe Yang , View ORCID Profile Youjun Wu , Sanjoy Mehta , View ORCID Profile Aaron Zhong , View ORCID Profile Elena Grossi , View ORCID Profile Richard P Koche , View ORCID Profile Valentina Kirigin Callau , View ORCID Profile Ryan M Walsh , View ORCID Profile Alessandro Evangelisti , View ORCID Profile Yujie Fan , View ORCID Profile Emily Bernstein , View ORCID Profile Ralph J Garippa , View ORCID Profile Lincon A Stamp , View ORCID Profile Marlene M Hao , Ting Zhou , View ORCID Profile Lorenz O.S. Studer doi: https://doi.org/10.64898/2026.10.17.759682 James O.S. Hackland 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for James O.S. Hackland Giridhar Anand 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Giridhar Anand Ragavi Vijayakumar 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ragavi Vijayakumar Xiaoyi Wang 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Xiaoyi Wang Vittoria Dickinson Bocchi 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vittoria Dickinson Bocchi Eve S Rowland 2 University of Melbourne; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eve S Rowland Donghe Yang 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Donghe Yang Youjun Wu 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Youjun Wu Sanjoy Mehta 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aaron Zhong 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Aaron Zhong Elena Grossi 3 European Institute of Oncology (IEO) IRCCS; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Elena Grossi Richard P Koche 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Richard P Koche Valentina Kirigin Callau 4 Icahn School of Medicine at Mount Sinai; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Valentina Kirigin Callau Ryan M Walsh 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ryan M Walsh Alessandro Evangelisti 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alessandro Evangelisti Yujie Fan 5 Caltech Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yujie Fan Emily Bernstein 4 Icahn School of Medicine at Mount Sinai; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Emily Bernstein Ralph J Garippa 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ralph J Garippa Lincon A Stamp 2 University of Melbourne; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lincon A Stamp Marlene M Hao 2 University of Melbourne; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marlene M Hao Ting Zhou 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Lorenz O.S. Studer 1 Memorial Sloan Kettering Cancer Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lorenz O.S. Studer For correspondence: studerl{at}mskcc.org Abstract Info/History Metrics Supplementary material Preview PDF Abstract The vertebrate nervous system develops into functionally distinct domains along the body axis[1]. Developmental studies implicate multiple signaling pathways in coordinating this process, but the order of specification events, sufficiency of individual signals, and molecular basis of competency remain unclear [2,3], leaving the field without a unified model of neuraxis patterning. Enteric nervous system (ENS) and midbrain dopaminergic (mDA) progenitors have reached clinical and preclinical testing [4-11], yet neither is produced at full purity, and yields vary markedly across human pluripotent stem cell (hPSC) lines, reflecting incomplete control of axial identity. Here we use single-cell genetic fate mapping to demonstrate that hPSCs can commit to anterior or posterior cranial fate within the first 24 hours of differentiation, before neural induction. Building on this finding, we show that the duration of a single saturating WNT pulse is sufficient to specify three 'first-order' domains: anterior cranial (0 h), posterior cranial (24 h) and trunk (48 h), each pre-neural and competent for CNS, neural crest and epidermal lineages. Nested 'second-order' domains are specified within first-order domains in response to WNT, FGF, and retinoic acid. Mechanistically, an anterior gene regulatory network repressing WNT targets is irreversibly shut down during the transition to posterior identities. Applying this binary WNT patterning logic, we generate mDA neurons and ENS progenitors robustly across hPSC lines and establish an assembloid model combining first-order progenitors to produce all major regions of the nervous system. Competing Interest Statement Memorial Sloan Kettering Cancer Center has filed two patent applications (U.S. Application No.:63/735,067 and 63/735,043) related to the methods of deriving and using midbrain dopamine neuron subtypes, and hindbrain-level derivatives respectively with J.O.S.H. and L.S. as inventors. L.S. is a scientific founder and consultant of BlueRock Therapeutics and DaCapo Brainscience. All other authors do not declare any competing interests. Funder Information Declared National Institute of Neurological Disorders and Stroke , R01NS099270 , R01NS118067 Eunice Kennedy Shriver National Institute of Child Health and Human Development , R21HD112917 NIH/NCI Cancer Center Support Grant , P30 CA0088748 The Michael J Fox Foundation , MJFF-026800 MSKCC-Therapeutic Development Fund Freedom Together Foundation (FTF) Parkinson's Foundation Launch Award , PF-LAUNCH-1584415 Horizon MSCA , HORIZON-MSCA-2024-PF-01: 101203036 BlueRock Therapeutics , SK2018-1304 Australian NHMRC MRFF Stem Cell Therapies Mission , 2032801 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted October 20, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Timed binary WNT activity is sufficient to model the early human neural axis Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Timed binary WNT activity is sufficient to model the early human neural axis James O.S. Hackland , Giridhar Anand , Ragavi Vijayakumar , Xiaoyi Wang , Vittoria Dickinson Bocchi , Eve S Rowland , Donghe Yang , Youjun Wu , Sanjoy Mehta , Aaron Zhong , Elena Grossi , Richard P Koche , Valentina Kirigin Callau , Ryan M Walsh , Alessandro Evangelisti , Yujie Fan , Emily Bernstein , Ralph J Garippa , Lincon A Stamp , Marlene M Hao , Ting Zhou , Lorenz O.S. Studer bioRxiv 2026.10.17.759682; doi: https://doi.org/10.64898/2026.10.17.759682 Share This Article: Copy Citation Tools Timed binary WNT activity is sufficient to model the early human neural axis James O.S. Hackland , Giridhar Anand , Ragavi Vijayakumar , Xiaoyi Wang , Vittoria Dickinson Bocchi , Eve S Rowland , Donghe Yang , Youjun Wu , Sanjoy Mehta , Aaron Zhong , Elena Grossi , Richard P Koche , Valentina Kirigin Callau , Ryan M Walsh , Alessandro Evangelisti , Yujie Fan , Emily Bernstein , Ralph J Garippa , Lincon A Stamp , Marlene M Hao , Ting Zhou , Lorenz O.S. 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