Activation of Six1 target genes is required for sensory placode formation

In vertebrates, cranial placodes form crucial parts of the sensory nervous system in the head. All cranial placodes arise from a common territory, the preplacodal region, and are identified by the expression of Six1/4 and Eya1/2 genes, which control different aspects of sensory development in invertebrates as well as vertebrates. While So and Eya can induce ectopic eyes in Drosophila, the ability of their vertebrate homologues to induce placodes in non-placodal ectoderm has not been explored. Here we show that Six1 and Eya2 are involved in ectodermal patterning and cooperate to induce preplacodal gene expression, while repressing neural plate and neural crest fates. However, they are not sufficient to induce ectopic sensory placodes in future epidermis. Activation of Six1 target genes is required for expression of preplacodal genes, for normal placode morphology and for placode-specific Pax protein expression. These findings suggest that unlike in the fly where the Pax6 homologue Eyeless acts upstream of Six and Eya, the regulatory relationships between these genes are reversed in early vertebrate placode development.     

A balance of FGF, BMP and WNT signalling positions the future placode territory in the head

The sensory nervous system in the vertebrate head arises from two different cell populations: neural crest and placodal cells. By contrast, in the trunk it originates from neural crest only. How do placode precursors become restricted exclusively to the head and how do multipotent ectodermal cells make the decision to become placodes or neural crest? At neural plate stages, future placode cells are confined to a narrow band in the head ectoderm, the pre-placodal region (PPR). Here, we identify the head mesoderm as the source of PPR inducing signals, reinforced by factors from the neural plate. We show that several independent signals are needed: attenuation of BMP and WNT is required for PPR formation. Together with activation of the FGF pathway, BMP and WNT antagonists can induce the PPR in na?ve ectoderm. We also show that WNT signalling plays a crucial role in restricting placode formation to the head. Finally, we demonstrate that the decision of multipotent cells to become placode or neural crest precursors is mediated by WNT proteins: activation of the WNT pathway promotes the generation of neural crest at the expense of placodes. This mechanism explains how the placode territory becomes confined to the head, and how neural crest and placode fates diversify.     

Neural crest and placode interaction during the development of the cranial sensory system

In the vertebrate head, the peripheral components of the sensory nervous system are derived from two embryonic cell populations, the neural crest and cranial sensory placodes. Both arise in close proximity to each other at the border of the neural plate: neural crest precursors abut the future central nervous system, while placodes originate in a common preplacodal region slightly more lateral. During head morphogenesis, complex events organise these precursors into functional sensory structures, raising the question of how their development is coordinated. Here we review the evidence that neural crest and placode cells remain in close proximity throughout their development and interact repeatedly in a reciprocal manner. We also review recent controversies about the relative contribution of the neural crest and placodes to the otic and olfactory systems. We propose that a sequence of mutual interactions between the neural crest and placodes drives the coordinated morphogenesis that generates functional sensory systems within the head.     

Neural crest and placode roles in formation and patterning of cranial sensory ganglia in lamprey

Vertebrates possess paired cranial sensory ganglia derived from two embryonic cell populations, neural crest and placodes. Cranial sensory ganglia arose prior to the divergence of jawed and jawless vertebrates, but the developmental mechanisms that facilitated their evolution are unknown. Using gene expression and cell lineage tracing experiments in embryos of the sea lamprey, Petromyzon marinus, we find that in the cranial ganglia we targeted, development consists of placode‐derived neuron clusters in the core of ganglia, with neural crest cells mostly surrounding these neuronal clusters. To dissect functional roles of neural crest and placode cell associations in these developing cranial ganglia, we used CRISPR/Cas9 gene editing experiments to target genes critical for the development of each population. Genetic ablation of SoxE2 and FoxD‐A in neural crest cells resulted in differentiated cranial sensory neurons with abnormal morphologies, whereas deletion of DlxB in cranial placodes resulted in near‐total loss of cranial sensory neurons. Taken together, our cell‐lineage, gene expression, and gene editing results suggest that cranial neural crest cells may not be required for cranial ganglia specification but are essential for shaping the morphology of these sensory structures. We propose that the association of neural crest and placodes in the head of early vertebrates was a key step in the organization of neurons and glia into paired sensory ganglia.     

Early development of the cranial sensory nervous system: from a common field to individual placodes

Sensory placodes are unique columnar epithelia with neurogenic potential that develop in the vertebrate head ectoderm next to the neural tube. They contribute to the paired sensory organs and the cranial sensory ganglia generating a wide variety of cell types ranging from lens fibres to sensory receptor cells and neurons. Although progress has been made in recent years to identify the molecular players that mediate placode specification, induction and patterning, the processes that initiate placode development are not well understood. One hypothesis suggests that all placode precursors arise from a common territory, the pre-placodal region, which is then subdivided to generate placodes of specific character. This model implies that their induction begins through molecular and cellular mechanisms common to all placodes. Embryological and molecular evidence suggests that placode induction is a multi-step process and that the molecular networks establishing the pre-placodal domain as well as the acquisition of placodal identity are surprisingly similar to those used in Drosophila to specify sensory structures.     

Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial muscle precursors

We cloned two isoforms of the Xenopus Eya1 orthologue. They show identical patterns of expression that closely resemble the previously described expression of XSix1, but partly differ from the expression of Eya1 in other vertebrates. XEya1 is expressed in the somites and hypaxial muscle precursors, but not in the pronephros. Moreover, all ectodermal placodes except the lens placode strongly express XEya1. At neural plate stages, ectodermal XEya1 expression starts in two domains, the anterior neural folds and a domain lateral to the neural folds. At tailbud stages, XEya1 expression continues in the adenohypophysis, all neurogenic placodes and placodally-derived structures including cranial ganglia, the otic vesicle and lateral line primordia.     

Lateral line, otic and epibranchial placodes: developmental and evolutionary links?

Two embryonic cell populations, the neural crest and cranial ectodermal placodes, between them give rise to many of the unique characters of vertebrates. Neurogenic placode derivatives are vital for sensing both external and internal stimuli. In this speculative review, we discuss potential developmental and evolutionary relationships between two placode series that are usually considered to be entirely independent: lateral line placodes, which form the mechanosensory and electroreceptive hair cells of the anamniote lateral line system as well as their afferent neurons, and epibranchial placodes (geniculate, petrosal and nodose), which form Phox2b(+) visceral sensory neurons with input from both the external and internal environment. We illustrate their development using molecular data we recently obtained in shark embryos, and we describe their derivatives, including the possible geniculate placode origin of a mechanosensory sense organ associated with the first pharyngeal pouch/cleft (the anamniote spiracular organ/amniote paratympanic organ). We discuss how both lateral line and epibranchial placodes can be related in different ways to the otic placode (which forms the inner ear and its afferent neurons), and how both are important for protective somatic reflexes. Finally, we put forward a highly speculative proposal about the original function of the cells whose evolutionary descendants today include the derivatives of the lateral line, otic and epibranchial placodes, namely that they produced sensory receptors and neurons for Phox2b-dependent protective reflex circuits. We hope this review will stimulate both debate and a fresh look at possible developmental and evolutionary relationships between these seemingly disparate and independent placodes.     

Gonadotropin-releasing hormone (GnRH) cells arise from cranial neural crest and adenohypophyseal regions of the neural plate in the zebrafish,Danio rerio

The olfactory placodes generate the primary sensory neurons of the olfactory sensory system. Additionally, the olfactory placodes have been proposed to generate a class of neuroendocrine cells containing gonadotropin-releasing hormone (GnRH). GnRH is a multifunctional decapeptide essential for the development of secondary sex characteristics in vertebrates as well as a neuromodulator within the central nervous system. Here, we show that endocrine and neuromodulatory GnRH cells arise from two separate, nonolfactory regions in the developing neural plate. Specifically, the neuromodulatory GnRH cells of the terminal nerve arise from the cranial neural crest, and the endocrine GnRH cells of the hypothalamus arise from the adenohypophyseal region of the developing anterior neural plate. Our findings are consistent with cell types generated by the adenohypophysis, a source of endocrine tissue in vertebrate animals, and by neural crest, a source of cells contributing to the cranial nerves. The adenohypophysis arises from a region of the anterior neural plate flanked by the olfactory placode fields at early stages of development, and premigratory cranial neural crest lies adjacent to the caudal edge of the olfactory placode domain [Development 127 (2000), 3645]. Thus, the GnRH cells arise from tissue closely associated with the developing olfactory placode, and their different developmental origins reflect their different functional roles in the adult animal.