Development
Author: Maria Belen Favarolo | Email: mfavarolo@fmed.uba.ar
M. Belen Favarolo1°, Micaela Garcia1°, Mariana Holubiec1°, Matias J. Garavaglia2°, Silvia L. Lopez1°
1° Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis” (IBCN). Universidad de Buenos Aires, Facultad de Medicina (UBA-CONICET).
2° Instituto de Biotecnología. Universidad Nacional de Hurlingham.
Neural induction occurs during gastrulation, when germ layers (ectoderm, mesoderm, and endoderm) arise. The neural tube develops from the induced neural ectoderm, where neurogenesis gives rise to neurons in a temporal and spatial orchestrated way. The Notch pathway, highly conserved through the animal kingdom, is a key player during neurogenesis, acting through lateral inhibition to prevent equipotent cells from simultaneously adopting the neuronal fate. Notch is a single-pass membrane receptor that, upon interaction with specific ligands presented by neighboring cells, undergoes sequential cleavages. In the last one, γ-secretase releases the Notch intracellular domain, which translocates to the nucleus, leading to transcriptional activation of target genes. Bisphenol A (BPA) is widely used to produce polycarbonate plastics. It is being recognized as an endocrine disruptor and related to perturbations of embryonic development. It was proposed as a γ-secretase inhibitor causing malformations in Xenopus laevis tadpoles. However, there is no previous work studying BPA exposure during early stages of development including neural induction. Here, we found that early exposure of X. laevis embryos to BPA delays neural plate folding and increases the density of differentiated neurons at neurula stage. Later consequences of early BPA exposure in tadpoles include microcephaly, shorter distance between eyes, misplacement of neural crest derivatives, and a shorter cephalo-caudal axis.