The peripheral sensory nervous system in the vertebrate head: A gene regulatory perspective

Abstract

In the vertebrate head, crucial parts of the sense organs and sensory ganglia develop from special regions, the cranial placodes. Despite their cellular and functional diversity, they arise from a common field of multipotent progenitors and acquire distinct identity later under the influence of local signalling. Here we present the gene regulatory network that summarises our current understanding of how sensory cells are specified, how they become different from other ectodermal derivatives and how they begin to diversify to generate placodes with different identities. This analysis reveals how sequential activation of sets of transcription factors subdivides the ectoderm over time into smaller domains of progenitors for the central nervous system, neural crest, epidermis and sensory placodes. Within this hierarchy the timing of signalling and developmental history of each cell population is of critical importance to determine the ultimate outcome. A reoccurring theme is that local signals set up broad gene expression domains, which are further refined by mutual repression between different transcription factors. The Six and Eya network lies at the heart of sensory progenitor specification. In a positive feedback loop these factors perpetuate their own expression thus stabilising pre-placodal fate, while simultaneously repressing neural and neural crest specific factors. Downstream of the Six and Eya cassette, Pax genes in combination with other factors begin to impart regional identity to placode progenitors. While our review highlights the wealth of information available, it also points to the lack information on the cis-regulatory mechanisms that control placode specification and of how the repeated use of signalling input is integrated.

Establishing neural crest identity: a gene regulatory recipe

“…These genes are activated by lateral neural plate border specifiers (Foxi1/3, Gata2/3 and Dlx5/6) (Fig. 4), which in turn regulate a number of transcription factors resulting in specification of the ectodermal placodes (Grocott et al, 2012;Sato et al, 2010). Similar to events observed at the neural/non-neural border, neural crest and preplacodal genes engage in a number of inhibitory interactions, which operate to molecularly segregate these two populations.…”

“…Tfap2a seems to be a key activator of neural plate border specifiers, also being required for the expression of Foxi genes and gata2/3 in zebrafish (Bhat et al, 2013). The more lateral neural plate border genes (Dlx5/6, Gata2/3 and Foxi1/3) also positively regulate each other in multiple positive regulatory loops (McLarren et al, 2003;Matsuo-Takasaki et al, 2005;Kwon et al, 2010; reviewed by Grocott et al, 2012). Such interactions lock down the regulatory state and allow for the maintenance of expression of neural plate border specifiers, which are often retained in the developing progenitors through later stages of development.…”

Nodal signaling regulates specification of ascidian peripheral neurons through control of the BMP signal

“…Snail family), pre-placodal specifiers (e.g. Six and Eya family) and inductive signaling molecules such as bone morphogenetic protein (BMP), fibroblast growth factor (FGF), Wnt and Notch (Grocott et al, 2012;Meulemans and BronnerFraser, 2004). Moreover, comparison of protochordate and vertebrate gene expression patterns suggests that the neural crest and neurogenic placodes did not arise de novo in vertebrates, but originated from the neural plate border in the common ancestor of protochordates and vertebrates (Imai et al, 2004;Mazet et al, 2005;Sauka-Spengler et al, 2007;Yu et al, 2008).…”

Illustrated Review of the Embryology and Development of the Facial Region, Part 3: An Overview of the Molecular Interactions Responsible for Facial Development

“…What is starting to be defined is a complex regulatory network that controls these events; and within this network, each step in the temporal hierarchy can be identified by a specific set of transcription factors that cross-regulate each other and that, in turn, are controlled by defined signaling inputs. 15 Thus, facial patterning is controlled by complex and coordinated signaling between the mesenchyme and epithelium. However, the precise roles of these tissues remain incompletely understood.…”