A single-cell time-lapse of mouse prenatal development from gastrula to birth.

The house mouse (Mus musculus) is an exceptional model system, combining genetic tractability with close evolutionary affinity to humans1,2. Mouse gestation lasts only 3 weeks, during which the genome orchestrates the astonishing transformation of a single-cell zygote into a free-living pup composed of more than 500 million cells. Here, to establish a global framework for exploring mammalian development, we applied optimized single-cell combinatorial indexing3 to profile the transcriptional states of 12.4 million nuclei from 83 embryos, precisely staged at 2- to 6-hour intervals spanning late gastrulation (embryonic day 8) to birth (postnatal day 0). From these data, we annotate hundreds of cell types and explore the ontogenesis of the posterior embryo during somitogenesis and of kidney, mesenchyme, retina and early neurons. We leverage the temporal resolution and sampling depth of these whole-embryo snapshots, together with published data4-8 from earlier timepoints, to construct a rooted tree of cell-type relationships that spans the entirety of prenatal development, from zygote to birth. Throughout this tree, we systematically nominate genes encoding transcription factors and other proteins as candidate drivers of the in vivo differentiation of hundreds of cell types. Remarkably, the most marked temporal shifts in cell states are observed within one hour of birth and presumably underlie the massive physiological adaptations that must accompany the successful transition of a mammalian fetus to life outside the womb.

Development and regeneration of the vagus nerve.

The vagus nerve, with its myriad constituent axon branches and innervation targets, has long been a model of anatomical complexity in the nervous system. The branched architecture of the vagus nerve is now appreciated to be highly organized around the topographic and/or molecular identities of the neurons that innervate each target tissue. However, we are only just beginning to understand the developmental mechanisms by which heterogeneous vagus neuron identity is specified, patterned, and used to guide the axons of particular neurons to particular targets. Here, we summarize our current understanding of the complex topographic and molecular organization of the vagus nerve, the developmental basis of neuron specification and patterned axon guidance that supports this organization, and the regenerative mechanisms that promote, or inhibit, the restoration of vagus nerve organization after nerve damage. Finally, we highlight key unanswered questions in these areas and discuss potential strategies to address these questions.