XB-ART-57058Dev Biol July 15, 2020; 463 (2): 169-181.
The transcription factor Hypermethylated in Cancer 1 (Hic1) regulates neural crest migration via interaction with Wnt signaling.
The transcription factor Hypermethylated in Cancer 1 (HIC1) is associated with both tumorigenesis and the complex human developmental disorder Miller-Dieker Syndrome. While many studies have characterized HIC1 as a tumor suppressor, HIC1 function in development is less understood. Loss-of-function mouse alleles show embryonic lethality accompanied with developmental defects, including craniofacial abnormalities that are reminiscent of human Miller-Dieker Syndrome patients. However, the tissue origin of the defects has not been reported. In this study, we use the power of the Xenopus laevis model system to explore Hic1 function in early development. We show that hic1 mRNA is expressed throughout early Xenopus development and has a spatial distribution within the neural plate border and in migrating neural crest cells in branchial arches. Targeted manipulation of hic1 levels in the dorsal ectoderm that gives rise to neural and neural crest tissues reveals that both overexpression and knockdown of hic1 result in craniofacial defects with malformations of the craniofacial cartilages. Neural crest specification is not affected by altered hic1 levels, but migration of the cranial neural crest is impaired both in vivo and in tissue explants. Mechanistically, we find that Hic1 regulates cadherin expression profiles and canonical Wnt signaling. Taken together, these results identify Hic1 as a novel regulator of the canonical Wnt pathway during neural crest migration.
PubMed ID: 32502469
PMC ID: PMC7437249
Article link: Dev Biol
Genes referenced: apc axin2 cdh1 cdh11 cdh2 ctnnb1 foxd3 hic1 krt70 msx1 snai1 snai2 sox10 sox2 tfap2a yap1
GO keywords: neural crest cell migration
Antibodies: Ctnnb1 Ab7 HA Ab3
Morpholinos: hic1 MO1
Disease Ontology terms: Miller-Dieker lissencephaly syndrome
OMIMs: MILLER-DIEKER LISSENCEPHALY SYNDROME; MDLS
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