Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family 
Flaviviridae) and was first described in 1947 in Uganda following blood analyses 
of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian 
lineages of the virus did not cause meaningful infections in humans. However, in 
2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy 
epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, 
arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus 
caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, 
ZIKV reached Brazil, later spreading to other countries in South and Central 
America. In Brazil, the virus has been linked to congenital malformations, 
including microcephaly and other severe neurological diseases, such as 
Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof 
showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains 
absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine 
growth restriction, including signs of microcephaly, in mice. Moreover, the 
virus infects human cortical progenitor cells, leading to an increase in cell 
death. We also report that the infection of human brain organoids results in a 
reduction of proliferative zones and disrupted cortical layers. These results 
indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting 
cortical progenitor cells, inducing cell death by apoptosis and autophagy, and 
impairing neurodevelopment. Our data reinforce the growing body of evidence 
linking the ZIKV(BR) outbreak to the alarming number of cases of congenital 
brain malformations. Our model can be used to determine the efficiency of 
therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human 
neurodevelopment.