scRNA-sequencing in chick suggests a probabilistic model for cell fate allocation at the neural plate border.

The vertebrate 'neural plate border' is a transient territory located at the edge of the neural plate containing precursors for all ectodermal derivatives: the neural plate, neural crest, placodes and epidermis. Elegant functional experiments in a range of vertebrate models have provided an in-depth understanding of gene regulatory interactions within the ectoderm. However, these experiments conducted at tissue level raise seemingly contradictory models for fate allocation of individual cells. Here, we carry out single cell RNA sequencing of chick ectoderm from primitive streak to neurulation stage, to explore cell state diversity and heterogeneity. We characterise the dynamics of gene modules, allowing us to model the order of molecular events which take place as ectodermal fates segregate. Furthermore, we find that genes previously classified as neural plate border 'specifiers' typically exhibit dynamic expression patterns and are enriched in either neural, neural crest or placodal fates, revealing that the neural plate border should be seen as a heterogeneous ectodermal territory and not a discrete transitional transcriptional state. Analysis of neural, neural crest and placodal markers reveals that individual NPB cells co-express competing transcriptional programmes suggesting that their ultimate identify is not yet fixed. This population of 'border located undecided progenitors' (BLUPs) gradually diminishes as cell fate decisions take place. Considering our findings, we propose a probabilistic model for cell fate choice at the neural plate border. Our data suggest that the probability of a progenitor's daughters to contribute to a given ectodermal derivative is related to the balance of competing transcriptional programmes, which in turn are regulated by the spatiotemporal position of a progenitor.

Sox8 remodels the cranial ectoderm to generate the ear.

The vertebrate inner ear arises from a pool of progenitors with the potential to contribute to all the sense organs and cranial ganglia in the head. Here, we explore the molecular mechanisms that control ear specification from these precursors. Using a multiomics approach combined with loss-of-function experiments, we identify a core transcriptional circuit that imparts ear identity, along with a genome-wide characterization of noncoding elements that integrate this information. This analysis places the transcription factor Sox8 at the top of the ear determination network. Introducing Sox8 into the cranial ectoderm not only converts non-ear cells into ear progenitors but also activates the cellular programs for ear morphogenesis and neurogenesis. Thus, Sox8 has the unique ability to remodel transcriptional networks in the cranial ectoderm toward ear identity.

Cell fate decisions during the development of the peripheral nervous system in the vertebrate head.

Sensory placodes and neural crest cells are among the key cell populations that facilitated the emergence and diversification of vertebrates throughout evolution. Together, they generate the sensory nervous system in the head: both form the cranial sensory ganglia, while placodal cells make major contributions to the sense organs-the eye, ear and olfactory epithelium. Both are instrumental for integrating craniofacial organs and have been key to drive the concentration of sensory structures in the vertebrate head allowing the emergence of active and predatory life forms. Whereas the gene regulatory networks that control neural crest cell development have been studied extensively, the signals and downstream transcriptional events that regulate placode formation and diversity are only beginning to be uncovered. Both cell populations are derived from the embryonic ectoderm, which also generates the central nervous system and the epidermis, and recent evidence suggests that their initial specification involves a common molecular mechanism before definitive neural, neural crest and placodal lineages are established. In this review, we will first discuss the transcriptional networks that pattern the embryonic ectoderm and establish these three cell fates with emphasis on sensory placodes. Second, we will focus on how sensory placode precursors diversify using the specification of otic-epibranchial progenitors and their segregation as an example.