Establishing the pre-placodal region and breaking it into placodes with distinct identities

Abstract

Specialized sensory organs in the vertebrate head originate from thickenings in the embryonic ectoderm called cranial sensory placodes. These placodes, as well as the neural crest, arise from a zone of ectoderm that borders the neural plate. This zone separates into a precursor field for the neural crest that lies adjacent to the neural plate, and a precursor field for the placodes, called the pre-placodal region (PPR), that lies lateral to the neural crest. The neural crest domain and the PPR are established in response to signaling events mediated by BMPs, FGFs and Wnts, which differentially activate transcription factors in these territories. In the PPR, members of the Six and Eya families, act in part to repress neural crest specific transcription factors, thus solidifying a placode developmental program. Subsequently, in response to environmental cues the PPR is further subdivided into placodal territories with distinct characteristics, each expressing a specific repertoire of transcription factors that provide the necessary information for their progression to mature sensory organs. In this review we summarize recent advances in the characterization of the signaling molecules and transcriptional effectors that regulate PPR specification and its subdivision into placodal domains with distinct identities.

Keywords: BMP; Cranial sensory placodes; Eya; FGF; Gene regulatory network; Pax; Pre-placodal ectoderm; Six; Wnt.

Figure 1. Major subdivisions of the embryonic ectoderm

At gastrulation, the embryonic ectoderm is subdivided into two domains: the non-neuronal ectoderm and neural ectoderm. They give rise to the epidermis and central nervous system (CNS), respectively. At their boundary a third domain is subsequently generated, the neural border zone, which gives rise to two cell populations the neural crest and pre-placodal region. The pre-placodal region eventually segregates into individual cranial placodes: the adenohypophyseal, olfactory, lens, trigeminal, lateral line, otic and epibranchial placodes (from anterior to posterior).

Figure 2. Combinatorial expression of transcription factors during specification of the PPR and segregation of the sensory placodes

Once specified, the PPR becomes sequentially subdivided into incrementally smaller domains each expressing a specific repertoire of genes. Only a subset of these genes is shown here. Anterior is to the left and posterior to the right.

Figure 3. Signaling pathways regulating placode formation

Diagram illustrating the signaling pathways involved in the specification of the PPR, and the subsequent step-wise induction of sensory placodes with distinct identities. The arrows indicate whether a signaling pathway is activated (↑) or inhibited (↓). BMP, bone morphogenetic protein; FGF, fibroblast growth factor; NOC, nociceptin; PDGF, platelet derived growth factor; RA, retinoic acid; SHH, sonic hedgehog; STT, somatostatin. Anterior is to the left and posterior to the right.