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

Department of Craniofacial Development and Stem Cell Biology, King's College London, Guy's Tower Wing, Floor 27, London SE1 9RT, UK.
Developmental Biology (Impact Factor: 3.55). 07/2012; 370(1):3-23. DOI: 10.1016/j.ydbio.2012.06.028
Source: PubMed


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.

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    • "In brief, the ectoderm differentiates into the neural ectoderm and nonneural ectoderm following the formation of the three germ layers [26]. Following this, rostral ectodermal cells next to the neuroectoderm differentiate into the preplacodal ectoderm [13] containing precursors for various sensory placodes, including the otic placode [7]. After otic placode induction from a region of the preplacodal ectoderm [6] [10], the otic placode invaginates and forms the otic vesicle by pinching off from the surface ectoderm [22]. "
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    ABSTRACT: Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 05/2015; 599. DOI:10.1016/j.neulet.2015.05.032 · 2.03 Impact Factor
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    • "As optic vesicle invagination occurs, the periocular mesenchyme that lies between the optic vesicle and surface ectoderm is excluded. Inductive signaling events (Charlton-Perkins, Brown, & Cook, 2011; Grocott, Tambalo, & Streit, 2012; Gunhaga, 2011; Lang, 2004; Shaham, Figure 1 Drawing describing the basic features of eye morphogenesis. (A) At E9.5 in the mouse, the optic stalk (os) and optic vesicle (ov) have evaginated from the diencephalic neural tube (nt) and approached the overlying surface ectoderm (se). "
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    ABSTRACT: Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. © 2015 Elsevier Inc. All rights reserved.
    Current Topics in Developmental Biology 02/2015; 111:375-99. DOI:10.1016/bs.ctdb.2014.11.011 · 4.68 Impact Factor
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    • "For example, 11/11 are expressed in the cleavage and blastula precursors of the ectoderm, which do not express Six1 (Pandur and Moody, 2000). In addition, at later stages 11/11 are expressed in the epidermis and neural tube; these results are consistent with gain-of-function studies in chick and frog showing that when Six1 is ectopically expressed it represses genes characteristic of these tissues (reviewed in Grocott et al., 2012; Saint-Jeannet and Moody, 2014). However, inconsistent with this expectation, most of the putative down-regulated genes are also expressed in the PPR, placodes (including otocyst), neural crest, somites, and nephric mesoderm. "
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    ABSTRACT: Background Six1 plays an important role in the development of several vertebrate organs, including cranial sensory placodes, somites and kidney. Although Six1 mutations cause one form of Branchio-Otic Syndrome (BOS), the responsible gene in many patients has not been identified; genes that act downstream of Six1 are potential BOS candidates.ResultsWe sought to identify novel genes expressed during placode, somite and kidney development by comparing gene expression between control and Six1-expressing ectodermal explants. The expression patterns of 19 of the significantly up-regulated and 11 of the significantly down-regulated genes were assayed from cleavage to larval stages. 28/30 genes are expressed in the otocyst, a structure that is functionally disrupted in BOS, and 26/30 genes are expressed in the nephric mesoderm, a structure that is functionally disrupted in the related Branchio-Otic-Renal (BOR) syndrome. We also identified the chick homologues of 5 genes and show that they have conserved expression patterns.Conclusions Of the 30 genes selected for expression analyses, all are expressed at many of the developmental times and appropriate tissues to be regulated by Six1. Many have the potential to play a role in the disruption of hearing and kidney function seen in BOS/BOR patients. This article is protected by copyright. All rights reserved.
    Developmental Dynamics 02/2015; 244(2). DOI:10.1002/dvdy.24229 · 2.38 Impact Factor
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