Sensory Organs: Making and Breaking the Pre‐Placodal Region

Sensory placodes are unique domains of thickened ectoderm in the vertebrate head that form important parts of the cranial sensory nervous system, contributing to sense organs and cranial ganglia. They generate many different cell types, ranging from simple lens fibers to neurons and sensory cells. Although progress has been made to identify cell interactions and signaling pathways that induce placodes at precise positions along the neural tube, little is known about how their precursors are specified. Here, we review the evidence that placodes arise from a unique territory, the pre‐placodal region, distinct from other ectodermal derivatives. We summarize the cellular and molecular mechanisms that confer pre‐placode character and differentiate placode precursors from future neural and neural crest cells. We then examine the events that subdivide the pre‐placodal region into individual placodes with distinct identity. Finally, we discuss the hypothesis that pre‐placodal cells have acquired a state of “placode bias” that is necessary for their progression to mature placodes and how such bias may be established molecularly.

Introduction

The “sensory placodes” were first described more than a century ago as localized thickenings in the cranial ectoderm of vertebrates (von Kupffer, 1891). Although placodal structures are also observed during formation of numerous other organs, such as teeth and hair, here we refer only to those that form crucial parts of the sensory nervous system. These sensory placodes contribute to the special sense organs (the olfactory epithelium, eye, and ear) and to the cranial sensory ganglia. Within these sensory structures, placode‐derived cells generate a vast array of functionally different cell types, which we describe briefly (extensive descriptions can be found in Baker 2001, Graham 2000, Webb 1993).

Three of the eight placodes give rise to both specialized receptor cells and the neurons that convey this sensory information to the central nervous system (CNS). The olfactory placode generates odorant‐ and pheromone‐sensing cells that populate the epithelium of the nose, and via the olfactory nerve, these primary sensory neurons directly project to the olfactory bulb of the telencephalon (Buck 2000, Couly 1985). Unlike other neurons, the olfactory receptor neurons in the nasal epithelium regenerate throughout life (Farbman, 1994). The olfactory placode is unique in that it generates glial cells, which ensheathe the olfactory and vomeronasal nerves (Couly 1985, Klein 1983). This placode also produces gonadotropin‐releasing hormone (GnRH)–secreting neurons that migrate to different positions in the CNS and ultimately control aspects of reproductive behavior (Dellovade 1998, Muske 1993, Schwanzel‐Fukuda 1989, Wray 1989).

The otic placode gives rise to the complex chambers of the inner ear and, within these structures, to various cell types including supporting and endolymph‐secreting cells, as well as the mechanosensory hair cells that detect acoustic and vestibular stimuli. The sensory neurons that innervate these receptor cells are also derived from the otic placode, their cell bodies being located in the acoustic and vestibular ganglia of the eighth cranial nerve. Unlike glial cells of the olfactory nerve, glial cells of the eighth nerve are of neural crest origin (D'Amico‐Martel and Noden, 1983).

The lateral line organs, found along the entire body of fish and aquatic amphibians, arise from two groups of placodes (one pre‐otic and one post‐otic) and are responsible for the detection of disturbances in the water, or weak electrical field changes. These organs are important for animal behavior, including prey detection, schooling behavior, and obstacle avoidance. Like the otic placode, lateral line placodes give rise to the sensory and to supporting cells in the ectoderm, as well as to the neurons that connect to the sensory cells (Northcutt and Brandle, 1995).

Two other groups of placodes also give rise to sensory neurons (but not to the actual sensory cells they innervate) and, together with neural crest cells, form cranial ganglia. Neuroblasts that delaminate from the trigeminal placode generate the trigeminal ganglion of the fifth cranial nerve, whose glial cells are of neural crest origin (D'Amico‐Martel and Noden, 1983). Axons projecting from this ganglion convey somatosensory information, including temperature, pain, and touch, from regions of the head such as the skin, jaws, and teeth (D'Amico‐Martel 1983, Schlosser 2000). At placode stages, the trigeminal primordium is subdivided into two molecularly distinct regions, the ophthalmic and the maxillomandibular placodes, reflecting the different targets that become innervated at a later stage by the trigeminal neurons (Baker 1999, Begbie 2002). The trigeminal ganglion initially comprises two lobes (ophthalmic and maxillomandibular), which in most craniates fuse at later stages (Northcutt 1995, Schlosser 2000).

The three epibranchial placodes (geniculate, petrosal, and nodose) give rise to the distal ganglia of the seventh, ninth, and tenth cranial nerves, respectively. Axons emanating from these ganglia convey viscerosensory and gustatory information from the oropharyngeal cavity, as well as the heart and other visceral organs. The proximal parts of these ganglia are of neural crest origin, as are the glial cells that envelop their axons (D'Amico‐Martel and Noden, 1983).

While all the placodes described so far generate neurons, the two remaining cranial placodes are nonneurogenic. The single adenohypophyseal placode located in the anterior midline gives rise to the endocrine cells of the adenohypophysis, the anterior component of the pituitary gland (Couly and Le Douarin, 1985). Finally, the lens placode forms the lens of the eye, although the simplicity of this structure belies the vital role it plays in eye development and function (Chow 2001, Cvekl 2004).

As illustrated in this brief summary, the various structures generated by cranial placodes are large and functionally diverse, as are the cell types that arise from them. Despite this they have been grouped into a family of structures with a presumed common developmental history (Baker 2001, Jacobson 1963, Northcutt 1983, Streit 2004). Indeed, they do share certain similarities, which seem to justify this grouping, including the formation of columnar epithelia, placode invagination (adenohypophysis, olfactory, lens, otic), and epithelial‐mesenchymal transition (i.e., delamination of neuroblasts). In addition, all placodes contribute to the cranial nervous system and are, with the exception of the lens and adenohypophysis, neurogenic. However, their structural and functional diversity raises the question of whether it is indeed useful to consider them as a homogeneous group (Begbie and Graham, 2001). If the sensory placodes are to be considered a “family,” then all members must share certain developmental traits, though dysfunctionality is allowed, because individual members may go on to adopt unique fates.

Thus, for the concept of the placodal family to prove valuable, two conditions must be met. First, all placode precursors should at some point of their development acquire unique properties—a “placodal ground state”—that distinguishes them from cells with other fates. For example, placodes are ectodermal derivatives, but so is the epidermis and the CNS. Therefore, “ectodermal character” cannot be considered a specific “placodal” trait, although it is an essential part of the “placodal family” program. Second, the “placodal ground state” should be a prerequisite for subsequent differentiation into any placode derivative. In other words, this state should represent a branch point in development through which all placode precursors must pass; thereafter, they may acquire distinct characteristics that identify them as specific placodes, such as otic or lens.

In this chapter, we summarize the evidence that supports the idea of a “pre‐placodal region” (PPR). We then review how this PPR is positioned and confined to the head ectoderm, in concert with the establishment of other ectodermal derivatives like the neural plate and the neural crest territory. We then discuss how the continuous pre‐placodal territory splits to form individual placodes. Finally, we return to the functional significance of the PPR and discuss the possibility that it represents a common “placode ground state.”