The mouse homeobox gene Otx2 plays essential roles at each step and in every tissue during head development. We have previously identified a series of enhancers that are responsible for driving the Otx2 expression in these contexts. Among them the AN enhancer, existing 92 kb 5' upstream, directs Otx2 expression in anterior neuroectoderm (AN) at the headfold stage. Analysis of the enhancer mutant Otx2(DeltaAN/-) indicated that Otx2 expression under the control of this enhancer is essential to the development of AN. This study demonstrates that the AN enhancer is promoter-dependent and regulated by acetylated YY1. YY1 binds to both the AN enhancer and promoter region. YY1 is acetylated in the anterior head, and only acetylated YY1 can bind to the sequence in the enhancer. Moreover, YY1 binding to both of these two sites is essential to Otx2 expression in AN. These YY1 binding sites are highly conserved in AN enhancers in tetrapods, coelacanth and skate, suggesting that establishment of the YY1 regulation coincides with that of OTX2 function in AN development in an ancestral gnathostome.
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http://dx.doi.org/10.1038/sj.emboj.7601619 | DOI Listing |
Dev Biol
January 2025
Institute of Life Sciences and Health (ILSH), School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK. Electronic address:
Conjoined twinning is a special case of monozygotic, monoamniotic twinning. Human conjoined twinning, and vertebrate conjoined twinning in general, is a very rare phenomenon. It has been suggested that the risk of conjoined twinning increases with some medication and upon assisted reproduction.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Developmental and Cell Biology, University of California, Irvine, CA, USA.
Functional analysis of non-coding variants associated with congenital disorders remains challenging due to the lack of efficient in vivo models. Here we introduce dual-enSERT, a robust Cas9-based two-color fluorescent reporter system which enables rapid, quantitative comparison of enhancer allele activities in live mice in less than two weeks. We use this technology to examine and measure the gain- and loss-of-function effects of enhancer variants previously linked to limb polydactyly, autism spectrum disorder, and craniofacial malformation.
View Article and Find Full Text PDFElife
December 2024
Department of Human Anatomy and Cell Science, The Children's Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium.
View Article and Find Full Text PDFSemin Ophthalmol
December 2024
Kallam Anji Reddy Molecular Genetics Laboratory, Prof. Brien Holden Eye Research Center, L V Prasad Eye Institute, Hyderabad, Telangana, India.
Background: The anterior segment of the eye plays a crucial role in maintaining the normal intraocular pressure and vision. Developmental defects in the anterior segment structures lead to anterior segment dysgenesis (ASD) and primary congenital glaucoma (PCG), which share overlapping clinical features. Several genes have been mapped and characterized in ASD, some of which are also involved in other glaucoma phenotypes.
View Article and Find Full Text PDFFront Cell Neurosci
November 2024
Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, United States.
Congenital ocular malformations originate from defective morphogenesis during early eye development and cause 25% of childhood blindness. Formation of the eye is a multi-step, dynamic process; it involves evagination of the optic vesicle, followed by distal and ventral invagination, leading to the formation of a two-layered optic cup with a transient optic fissure. These tissue folding events require extensive changes in cell shape and tissue growth mediated by cytoskeleton mechanics and intercellular adhesion.
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