ArticleCellular and molecular life sciences : CMLS2014
Combinatorial activity of Six1-2-4 genes in cephalic neural crest cells controls craniofacial and brain development.
Article in Cellular and molecular life sciences : CMLS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Pooled it
- ASH2L-mediated H3K4me3 methylation governs palatal development by regulating WNT5B.Epigenetics & chromatin · 2026Article
- Article
- The Emerging Roles of the Cephalic Neural Crest in Brain Development and Developmental Encephalopathies.International journal of molecular sciences · 2023Review
- Overlapping functions of SIX homeoproteins during embryonic myogenesis.PLoS genetics · 2023Article
- Review
- Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation.Frontiers in cell and developmental biology · 2022Article
- DNA-based eyelid trait prediction in Chinese Han population.International journal of legal medicine · 2021Article
- Shared heritability of human face and brain shape.Nature genetics · 2021Article
- Article
- ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum.Frontiers in genetics · 2021Article
- MicroRNA-23a inhibits endometrial cancer cell development by targeting SIX1.Oncology letters · 2019Article
- Crucial and Overlapping Roles of Six1 and Six2 in Craniofacial Development.Journal of dental research · 2019Article
- Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.EvoDevo · 2019Review
- Article
- Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division.Developmental biology · 2017Article
- Respective contribution of the cephalic neural crest and mesoderm to SIX1-expressing head territories in the avian embryo.BMC developmental biology · 2017Article
- Genetic advances in craniosynostosis.American journal of medical genetics. Part A · 2017Review
- Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2-associated Andersen-Tawil Syndrome.The Journal of physiology · 2016Article
- β-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis.BMC developmental biology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combinatorial expression of Hox genes is an evolutionarily ancient program underlying body axis patterning in all Bilateria. In the head, the neural crest (NC)--a vertebrate innovation that contributes to evolutionarily novel skeletal and neural features--develops as a structure free of Hox-gene expression. The activation of Hoxa2 in the Hox-free facial NC (FNC) leads to severe craniofacial and brain defects. Here, we show that this condition unveils the requirement of three Six genes, Six1, Six2, and Six4, for brain development and morphogenesis of the maxillo-mandibular and nasofrontal skeleton. Inactivation of each of these Six genes in FNC generates diverse brain defects, ranging from plexus agenesis to mild or severe holoprosencephaly, and entails facial hypoplasia or truncation of the craniofacial skeleton. The triple silencing of these genes reveals their complementary role in face and brain morphogenesis. Furthermore, we show that the perturbation of the intrinsic genetic FNC program, by either Hoxa2 expression or Six gene inactivation, affects Bmp signaling through the downregulation of Bmp antagonists in the FNC cells. When upregulated in the FNC, Bmp antagonists suppress the adverse skeletal and cerebral effects of Hoxa2 expression. These results demonstrate that the combinatorial expression of Six1, Six2, and Six4 is required for the molecular programs governing craniofacial and cerebral development. These genes are crucial for the signaling system of FNC origin, which regulates normal growth and patterning of the cephalic neuroepithelium. Our results strongly suggest that several congenital craniofacial and cerebral malformations could be attributed to Six genes' misregulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.