Investigating the role of sall4 during human cranial neural crest cells specification
File(s)
Author(s)
Demurtas, Martina
Type
Thesis or dissertation
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 strongly expressed in cranial neural crest cells (CNCCs) and associated with syndromes featuring craniofacial anomalies, plays a critical role in this early regulatory process. Using a SALL4-haploinsufficient human iPSC model that recapitulates clinical haploinsufficiency, we show that SALL4 directly interacts with BAF at the onset of CNCC induction, at the neuroectodermal stage. This interaction enables SALL4-mediated recruitment of BAF to CNCC-specific enhancers during early neural plate stages. Without functional SALL4, BAF fails to load at chromatin, leaving CNCC enhancers inaccessible despite normal neuroectodermal progression. Consequently, cells cannot undergo proper CNCC induction and specification due to persistent enhancer repression. Our findings reveal SALL4 as an essential regulator of BAF-dependent enhancer activation during early neural crest development, providing molecular insights into SALL4-associated craniofacial anomalies.
Version
Open Access
Date Issued
2025-12-23
Date Awarded
2026-07-01
Copyright Statement
Attribution-NonCommercial-ShareAlike 4.0 International Licence (CC BY NC-SA)
Advisor
Trizzino, Marco
Southall, Tony
Publisher Department
Department of Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)