Publications by authors named "Andre Landin-Malt"
Intercellular signaling mediated by evolutionarily conserved planar cell polarity (PCP) proteins aligns cell polarity along the tissue plane and drives polarized cell behaviors during tissue morphogenesis. Accumulating evidence indicates that the vertebrate PCP pathway is regulated by noncanonical, β-catenin-independent Wnt signaling; however, the signaling components and mechanisms are incompletely understood. In the mouse hearing organ, both PCP and noncanonical Wnt (ncWnt) signaling are required in the developing auditory sensory epithelium to control cochlear duct elongation and planar polarity of resident sensory hair cells (HCs), including the shape and orientation of the stereociliary hair bundle essential for sound detection.
View Article and Find Full Text PDFDuring development, sensory hair cells (HCs) in the cochlea assemble a stereociliary hair bundle on their apical surface with planar polarized structure and orientation. We have recently identified a non-canonical, Wnt/G-protein/PI3K signaling pathway that promotes cochlear outgrowth and coordinates planar polarization of the HC apical cytoskeleton and alignment of HC orientation across the cochlear epithelium. Here, we determined the involvement of the kinase Gsk3β and the small GTPase Rac1 in non-canonical Wnt signaling and its regulation of the planar cell polarity (PCP) pathway in the cochlea.
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- The planar cell polarity (PCP) pathway is crucial for aligning hair cells in the cochlea, while intrinsic planar polarity (iPCP) controls their internal structure and function.
- Genetic disruption of Wnt secretion in cochlear cells leads to impaired hair cell shape and orientation, affecting hearing abilities.
- Wnt proteins activate a signaling pathway involving Gi proteins and PI3K, which is essential for coordinating PCP and iPCP during cochlear development.
In the inner ear sensory epithelia, stereociliary hair bundles atop sensory hair cells are mechanosensory apparatus with planar polarized structure and orientation. This is established during development by the concerted action of tissue-level, intercellular planar cell polarity (PCP) signaling and a hair cell-intrinsic, microtubule-mediated machinery. However, how various polarity signals are integrated during hair bundle morphogenesis is poorly understood.
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- The calvaria, or upper part of the skull, develops from mesenchyme around the brain, with specific regions (like supra-orbital mesenchyme) promoting bone growth while others (early migrating mesenchyme) do not.
- Researchers discovered Lmx1b, a gene that acts as an anti-osteogenic factor in early migrating mesenchyme, helping to differentiate areas with varying capacities for bone development.
- Altering the expression of Lmx1b can lead to abnormal bone growth and conditions like craniosynostosis, highlighting its crucial role in the proper formation and organization of the skull.
TEAD proteins constitute a family of highly conserved transcription factors, characterized by a DNA-binding domain called the TEA domain and a protein-binding domain that permits association with transcriptional co-activators. TEAD proteins are unable to induce transcription on their own. They have to interact with transcriptional cofactors to do so.
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- Cleft palate is a common birth defect, and understanding its molecular genetics, specifically the roles of Lhx6 and Lhx8 genes, is crucial for science and medicine.
- In mice lacking Lhx6 and Lhx8, severe craniofacial issues arose, linked to impaired palate growth due to decreased cell proliferation, revealing the involvement of the cell cycle inhibitor p57(Kip2).
- The study demonstrates that Lhx6 and Lhx8 regulate p57(Kip2) through both direct and indirect mechanisms, highlighting a new pathway that connects cell proliferation and palate development.
Development of the mammalian face requires a large number of genes that are expressed with spatio-temporal specificity, and transcriptional regulation mediated by enhancers plays a key role in the precise control of gene expression. Using chromatin immunoprecipitation for a histone marker of active enhancers, we generated a genome-wide map of candidate enhancers from the maxillary arch (primordium for the upper jaw) of mouse embryos. Furthermore, we confirmed multiple novel craniofacial enhancers near the genes implicated in human palate defects through functional assays.
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- LDB1 is crucial for craniofacial development, specifically in forming the secondary palate, as shown in tissue-specific mutant mouse models.
- Mutant embryos with LDB1 deletion exhibited cleft palates and abnormal palatal shelf morphology due to defective elevation above the tongue and altered cell proliferation.
- The study highlights the role of LDB1 in regulating key developmental genes like Wnt5a, Pax9, and Osr2 necessary for normal palate morphogenesis.
Article Synopsis
- The NAIP gene is linked to preventing cell death (apoptosis) and inflammation, but how it is expressed is not well understood.
- Research shows that the TEA domain protein 1 (TEAD1) can activate the NAIP gene's expression, but it needs to interact with another protein called YAP.
- A specific region within the NAIP gene responds to the TEAD1/YAP interaction, indicating that this regulation happens during the gene's transcription process.
Background: TEA domain (TEAD) proteins are highly conserved transcription factors involved in embryonic development and differentiation of various tissues. More recently, emerging evidences for a contribution of these proteins towards apoptosis and cell proliferation regulation have also been proposed. These effects appear to be mediated by the interaction between TEAD and its co-activator Yes-Associated Protein (YAP), the downstream effector of the Hippo tumour suppressor pathway.
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