Document Type
Article
Publication Date
12-15-2025
Abstract
Neural crest induction begins early during neural plate formation, requiring precise transcriptional control to activate lineage-specific enhancers. Here, we demonstrate that SALL4, a transcription factor associated with syndromes featuring craniofacial anomalies, plays a crucial role in early cranial neural crest (CNCC) specification. Using SALL4-het-KO human iPSCs to model clinical haploinsufficiency, we show that SALL4 directly recruits BAF to CNCC-lineage specific enhancers at the neuroectodermal stage, specifically when neural crest gene expression is induced at the neural plate border. Without functional SALL4, BAF is not loaded at chromatin, leaving CNCC enhancers inaccessible. Consequently, the cells cannot undergo proper CNCC induction and specification due to persistent enhancer repression, despite normal neuroectodermal and neural plate progression. Moreover, by performing SALL4 isoform-specific depletion, we demonstrate that SALL4A is the isoform essential for CNCC induction and specification, and that SALL4B cannot compensate for SALL4A loss in this developmental process. In summary, our findings reveal SALL4 as essential regulator of BAF-dependent enhancer activation during early stages of neural crest development, providing molecular insights into SALL4-associated craniofacial anomalies.
Recommended Citation
Demurtas, Martina; Barnada, Samantha M.; van Domselaar, Emma; Mitchell, Zoe H.; Deelen, Laura; and Trizzino, Marco, "Neural Crest Induction Requires SALL4-Mediated Baf Recruitment to Lineage Specific Enhancers" (2025). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 292.
https://jdc.jefferson.edu/bmpfp/292
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Table S1. List of AlphaFold predicted contacts between SALL4A and DPF2..xlsx (72 kB)
Table S2. List of AlphaFold predicted contacts between SALL4B and DPF2..xlsx (55 kB)
Table S3. List of TPMs and DEGs (RNA-seq) for Day-0, Day-5, and Day14..xlsx (5309 kB)
Table S4. List of nearest genes to SALL4 CUT&RUN peaks and BRG1 ChIP-seq peaks..xlsx (7185 kB)
PubMed ID
41312722
Language
English
Comments
This article is the author's final published version in Development, Volume 152, Issue 24, December 2025, Article Number dev205248.
The published version is available at https://doi.org/10.1242/dev.205248. Copyright © 2025. Published by The Company of Biologists.