The transcription factor Pitx2 positions the embryonic axis and regulates twinning
| Autor: | Luz Mayela Soto-Jimenez, Nidia M.M. Oliveira, Alona Sosinsky, Ingrid Lekk, Angela Torlopp, Mohsin A.F. Khan, Claudio D. Stern |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Chromatin Immunoprecipitation
Growth Differentiation Factor 1 Time Factors animal structures Litter Size QH301-705.5 chicken Science Embryonic Development Chick Embryo Biology General Biochemistry Genetics and Molecular Biology GDF1 Avian Proteins Histones 03 medical and health sciences 0302 clinical medicine Endoderm formation Animals primitive streak gastrulation Biology (General) Enhancer In Situ Hybridization Oligonucleotide Array Sequence Analysis 030304 developmental biology Homeodomain Proteins Genetics 0303 health sciences General Immunology and Microbiology Primitive streak General Neuroscience Computational Biology Gene Expression Regulation Developmental General Medicine Gastrulation Enhancer Elements Genetic Developmental Biology and Stem Cells embryonic axis embryo polarity Medicine NODAL Developmental biology 030217 neurology & neurosurgery Protein Binding Transcription Factors Research Article |
| Zdroj: | eLife, Vol 3 (2014) eLife |
| Popis: | Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left–right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. DOI: http://dx.doi.org/10.7554/eLife.03743.001 eLife digest In warm-blooded animals, including chickens and humans, a single embryo can give rise to several separate individuals (identical twins). Some species of armadillos routinely give birth to quadruplets in this way—and in experiments, up to eight identical chick embryos can be produced by cutting one embryo into smaller pieces (a type of ‘experimental twinning’). This ability of a developing embryo to subdivide into separate individuals ends when the embryo starts to form its first midline structure, called the ‘primitive streak’. This is the first line of symmetry and defines where the head–tail axis will later develop. The steps that establish the axes of the embryo in birds and mammals, and the factors that prevent further splitting of the embryo to form twins after this point, are only just beginning to be understood. In chick embryos, the production of a protein called cVg1 is the first known step and precedes the development of a line of symmetry. A similar protein is produced in mammalian embryos and both proteins are members of an important family of signalling proteins. Now, Torlopp, Khan et al. have used a combination of techniques to search for other proteins that that control the production of the cVg1 protein. Genes that are active in the region of the embryo that will express cVg1 later in development were identified, both in normal embryos and during the process of experimental twinning. This search revealed Pitx2 as a protein that acts to switch on the expression of the gene that encodes cVg1. When the Pitx2 protein is removed, the embryonic axis forms from the opposite side. Next, Torlopp, Khan et al. searched the chicken genome to identify stretches of DNA around the cVg1 gene where proteins that regulate gene expression might bind. Six potential sites were found, including four to which Pitx2 can bind. Further experiments confirmed that two of these regulatory sequences encourage the expression of the cVg1 gene at its correct position in the embryo. Pitx2 and related proteins were known to be involved with the development of left–right symmetry later in development; the findings of Torlopp, Khan et al. reveal, unexpectedly, that these proteins are also involved in first establishing the position at which the midline of the embryo will arise. It remains unclear what prevents most embryos from forming twins. But Torlopp, Khan et al.'s findings could help to explain some strange observations, made long ago, about left–right asymmetry in identical twins. For example, they could help explain why one of the twins in an identical twin pair is more likely to be left-handed than an individual in the general population, and why the direction of whorls of hair on the back of the head is often mirrored between identical twins. DOI: http://dx.doi.org/10.7554/eLife.03743.002 |
| Databáze: | OpenAIRE |
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