Hernandez, J. C. | bioRxiv Science

bioRxiv2019

WNT/β-CATENIN modulates the axial identity of ES derived human neural crest

The WNT/{beta}-CATENIN pathway is critical for neural crest (NC) formation. However, the effects of the magnitude of the signal remains poorly defined. Here we evaluate the consequences of WNT magnitude variation in a robust model of human NC formation. This model is based on human embryonic stem cells induced by WNT signaling through the small molecule CHIR9902. In addition to its known effect on NC formation, we find that the WNT signal modulates the anterior-posterior axial identity of NCCs in a dose dependent manner, with low WNT leading to anterior OTX+, HOX-NC, and high WNT leading to posterior OTX-, HOX+ NC. Differentiation tests of posterior NC confirm expected derivatives including posterior specific adrenal derivatives, and display partial capacity to generate anterior ectomesenchymal derivatives. Furthermore, unlike anterior NC, posterior NC transit through a TBXT+/SOX2+ neuromesodermal precursor-like intermediate. Finally, we analyze the contributions of other signaling pathways in posterior NC formation, and suggest a critical role for FGF in survival/proliferation, and a requirement of BMP for NC maturation. As expected RA and FGF are able to modulate HOX expression in the posterior NC, but surprisingly, RA supplementation prohibits anterior, but only reduces, posterior NC formation. This work reveals for the first time that the amplitude of WNT signaling can modulate the axial identity of NC cells in humans.

developmental biology↗

bioRxiv2018

Mitogenomes illuminate the origin and migration patterns of the indigenous people of the Canary Islands

The Canary Islands indigenous people have been the subject of substantial archaeological, anthropological, linguistic and genetic research pointing to a most probable North African Berber source. However, neither agreement about the exact point of origin nor a model for the indigenous colonization of the islands has been established. To shed light on these questions, we analyzed 48 ancient mitogenomes from 25 archaeological sites from the seven main islands. Most lineages observed in the ancient samples have a Mediterranean distribution, and belong to lineages associated with the Neolithic expansion in the Near East and Europe (T2c, J2a, X3a...). This phylogeographic analysis of Canarian indigenous mitogenomes, the first of its kind, shows that some lineages are restricted to Central North Africa (H1cf, J2a2d and T2c1d3), while others have a wider distribution, including both West and Central North Africa, and, in some cases, Europe and the Near East (U6a1a1, U6a7a1, U6b, X3a, U6c1). In addition, we identify four new Canarian-specific lineages (H1e1a9, H4a1e, J2a2d1a and L3b1a12) whose coalescence dates correlate with the estimated time for the colonization of the islands (1st millennia CE). Additionally, we observe an asymmetrical distribution of mtDNA haplogroups in the ancient population, with certain haplogroups appearing more frequently in the islands closer to the continent. This reinforces results based on modern mtDNA and Y-chromosome data, and archaeological evidence suggesting the existence of two distinct migrations. Comparisons between insular populations show that some populations had high genetic diversity, while others were probably affected by genetic drift and/or bottlenecks. In spite of observing interinsular differences in the survival of indigenous lineages, modern populations, with the sole exception of La Gomera, are homogenous across the islands, supporting the theory of extensive human mobility after the European conquest.

genetics↗