The PrP prion protein is well known for its crucial role in transmissible encephalopathies and its implication in other amyloid-based neuro-degenerative diseases has recently been suggested. However, its physiological function remains poorly understood. The prion protein family is composed of three related genes. Both PrP and Shadoo share neuroprotective properties and are expressed in overlapping adult tissues. Doppel appears to be mostly involved in late spermatogenesis. Prion proteins have been shown to be involved in various adult stem cell self-renewal and/or differentiation, suggesting a role of these proteins in adult stem cell homeostasis. Recent data highlighted the crucial role of PrP1 and PrP2 in early embryogenesis of Zebrafish  and we recently discovered that of PrP, in conjunction with Shadoo, in early mouse embryonic development. Transcriptomic analyses revealed that in these distant species similar pathways might be affected by the disruption of these genes although the resulting phenotypes differed both in terms of developmental stage and location. This short review summarizes the recent data obtained on the prion protein implications in early embryonic animal development, highlighting species specificities and biological convergences.