2025/11/28 by Martina Demurtas, Samantha M. Barnada, Emma van Domselaar +3 · 2 voices · 2 citations
Biochemistry, Genetics and Molecular Biology · #Cranial neural crest #Developmental Biology and Gene Regulation #Enhancer #Neural crest #Neural development #Neural fold #Neural plate #Pluripotent Stem Cells Research #Regulator #Renal and related cancers #Transcription factor
paper · doi:10.1242/dev.205248
published in Development 152(24) (The Company of Biologists)
openalex created_date 2025/11/28 · openalex publication_date 2025/11/28 · openalex updated_date 2026/08/01
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.