The study investigates the role of Ambra1, a previously unknown protein with a WD40 domain, in autophagy and embryonic development. Ambra1 is identified as a positive regulator of Beclin1-dependent autophagy, as demonstrated by overexpression and RNA interference experiments. Deficiency in Ambra1 leads to severe neural tube defects, increased cell proliferation, excessive apoptosis, and accumulation of ubiquitinated proteins in mouse embryos. The results provide evidence for a complex interplay between autophagy, cell growth, and cell death during neural development in mammals. Additionally, the identification of Ambra1 as a vertebrate-specific autophagy regulator suggests its potential role in human congenital brain malformations and neurodegenerative disorders.The study investigates the role of Ambra1, a previously unknown protein with a WD40 domain, in autophagy and embryonic development. Ambra1 is identified as a positive regulator of Beclin1-dependent autophagy, as demonstrated by overexpression and RNA interference experiments. Deficiency in Ambra1 leads to severe neural tube defects, increased cell proliferation, excessive apoptosis, and accumulation of ubiquitinated proteins in mouse embryos. The results provide evidence for a complex interplay between autophagy, cell growth, and cell death during neural development in mammals. Additionally, the identification of Ambra1 as a vertebrate-specific autophagy regulator suggests its potential role in human congenital brain malformations and neurodegenerative disorders.