Jeramiah Smith, Weiming Li and colleagues report the whole-genome sequence of the sea lamprey, Petromyzon marinus, representing a vertebrate lineage diverged from humans ~500 million years ago. Their analyses define key evolutionary events in vertebrate lineages and provide evidence for two whole-genome duplication events occurring before the divergence of the ancestral lamprey and jawed vertebrate (gnathostome) lineages. Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.

▪ Abstract The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.

We investigated whether co‐expression of Neurog1 and Atoh1 in common neurosensory precursors could explain the loss of hair cells in Neurog1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base‐to‐apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex‐to‐base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog1 null mice show cell cycle exit in an apex‐to‐base progression about 1–2 days earlier. Atoh1 is expressed in an apex‐to‐base progression rather then a base‐to‐apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh1‐Cre lines. We show Atoh1‐Cre mediated β‐galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh1 in the otocyst as early as E10.5, prior to any histology‐based detection techniques. Combined, these data suggest that low levels of Atoh1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh1‐Cre expression in E18.5 embryos and P31 mice reveal β‐galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh1‐LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh1 expression in vestibular sensory neurons is confirmed with RT‐PCR. We propose that the absence of NEUROG1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia. Developmental Dynamics 234:633–650, 2005.

Sox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea.