Neurodevelopmental disorders affect one in one thousand births in the United States alone. While genetic and environmental factors drive normal development, they also have the potential to contribute to neurodevelopmental conditions such as microcephaly and neural tube defects (NTDs). This work has examined two of these factors: the RNA-binding protein Lin28, an important post-transcriptional regulator of neural progenitor cell (NPC) behaviors, and the Zika virus, an environmental cause of microcephaly. Lin28 and the Zika virus differentially impact the proliferative capacity of NPCs and the progression of brain development. I have characterized Lin28a/b mutant mice to determine Lin28s post-transcriptional regulatory role in NPCs. Lin28a/b mutants exhibit NTDs and decreased proliferative capacity. Combining a mouse model of reduced protein synthesis (Rpl24Bst/+) with Lin28a/b mutant and Lin28aOETg/+ overexpression, I discovered that Lin28A/B are required to promote protein synthesis during neurulation. Polysome-RNA sequencing studies identified biological mechanisms that were differentially regulated post-transcriptionally in Lin28a/b mutants, and showed that Lin28 promotes NPC proliferation in part by promoting ribosome biogenesis and cell cycle. This study has illuminated the importance and complexity of post-transcriptional regulation in neurodevelopment and suggests that regulators of translation may underlie yet undiscovered causes of NTDs.To understand how the Zika virus may cause microcephaly in humans, I first developed a model for Zika virus-induced microcephaly in rodents using intracerebral inoculation. In addition to causing microcephaly, massive brain damage, and disrupting NPC proliferation, the Zika virus disrupts the development of the neurovasculature and results in blood brain barrier leakage into the developing parenchyma. I also asked how the Zika virus became associated with causing neurodevelopmental defects only recently, considering it was first detected in 1947. In comparison studies between a 1947 African isolate and a 2016 Mexican isolate of the virus, I found that the African isolate caused more aggressive damage to the developing mouse brain than the more recent Mexican isolate, suggesting that the Zika virus has become less virulent over time. These experiments have identified novel mechanisms for Zika virus-induced neurodevelopmental disruption and provided the field with a better understanding of its virulence and potential therapeutic targets.