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Article Dans Une Revue Cell Death and Disease Année : 2019

Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs

Résumé

Head dysgenesis is a major cause of fetal demise and craniofacial malformation. Although mutations in genes of the head ontogenetic program have been reported, many cases remain unexplained. Head dysgenesis has also been related to trisomy or amplification of the chromosomal region overlapping the CDX2 homeobox gene, a master element of the trunk ontogenetic program. Hence, we investigated the repercussion on head morphogenesis of the imbalance between the head and trunk ontogenetic programs, by means of ectopic rostral expression of CDX2 at gastrulation. This caused severe malformations affecting the forebrain and optic structures, and also the frontonasal process associated with defects in neural crest cells colonization. These malformations are the result of the downregulation of genes of the head program together with the abnormal induction of trunk program genes. Together, these data indicate that the imbalance between the anterior and posterior ontogenetic programs in embryos is a new possible cause of head dysgenesis during human development, linked to defects in setting up anterior neuroectodermal structures.
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hal-03682397 , version 1 (31-05-2022)

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Emmanuelle Grall, Victor Gourain, Asmaa Naïr, Elisabeth Martin, Marie-Christine Birling, et al.. Severe head dysgenesis resulting from imbalance between anterior and posterior ontogenetic programs. Cell Death and Disease, 2019, 10 (11), pp.812. ⟨10.1038/s41419-019-2040-0⟩. ⟨hal-03682397⟩
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