Abstract:SummaryFew families of signaling factors have been implicated in the control of development. Here, we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in both chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors, with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin, and both peptides regulate … Show more
“…Transcripts associated with GO terms related to the acquisition of anterior character such as ‘eye, pituitary gland, nose, forebrain and diencephalon’ ( Pax6 , Otx1/2 , Mafa , Hesx1 , Pax3 , Dlx5 ; ) are significantly under-represented at the OEP stage (Fig. 3B,B′), consistent with the earlier suggestion that repression of anterior fate is an important step for otic induction (Bailey et al, 2006; Lleras-Forero and Streit, 2012). Fig.…”
The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition from progenitor to committed precursor, integrating known and novel molecular players. Our results not only characterize the otic transcriptome in unprecedented detail, but also identify new gene interactions responsible for inner ear development and for the segregation of the otic lineage from epibranchial progenitors. By recapitulating the embryonic programme, the genes and genetic sub-circuits discovered here might be useful for reprogramming naïve cells towards otic identity to restore hearing loss.
“…Transcripts associated with GO terms related to the acquisition of anterior character such as ‘eye, pituitary gland, nose, forebrain and diencephalon’ ( Pax6 , Otx1/2 , Mafa , Hesx1 , Pax3 , Dlx5 ; ) are significantly under-represented at the OEP stage (Fig. 3B,B′), consistent with the earlier suggestion that repression of anterior fate is an important step for otic induction (Bailey et al, 2006; Lleras-Forero and Streit, 2012). Fig.…”
The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition from progenitor to committed precursor, integrating known and novel molecular players. Our results not only characterize the otic transcriptome in unprecedented detail, but also identify new gene interactions responsible for inner ear development and for the segregation of the otic lineage from epibranchial progenitors. By recapitulating the embryonic programme, the genes and genetic sub-circuits discovered here might be useful for reprogramming naïve cells towards otic identity to restore hearing loss.
“…Data show a common pool of lens/olfactory progenitor cells and that formation of the olfactory cells requires transient inhibition of BMP signaling [24]. More recent studies identified two neuropeptides, nociceptin and somatostatin, as lens and olfactory placode inducing molecules in chicken [56]. Clonal analysis of cells comprising the aPPR identified a down-regulation of Dlx5 in the lens compared to the olfactory progenitor cells [57], Dlx5 + cells are ultimatelly excluded from the lens altogether [49].…”
Section: The “Invisible” and “Visible” Stages Of Lens Developmentmentioning
Ocular lens development represents an advantageous system to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and underlying gene regulatory networks. Spatiotemporaly regulated domains of BMP, FGF, and other signaling molecules in the late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate expression of the lens structural proteins, the crystallins. A multitude of cross-talks between a diverse array of signaling pathways control the complexity and order of the lens morphogenetic processes and its transparency.
“…A recent study has identified two neuropetides, Nociceptin and Somatostatin, controlling the specification of the anterior PPR in fish and chick (Llera-Forero et al, 2013). This study reports that mesendoderm-derived Somatostatin promotes ectodermal Nociceptin expression, and both peptides regulate Pax6 expression in lens and olfactory progenitors.…”
Section: Iv- Subdivision Of the Ppr Into Domains With Distinct Identimentioning
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 provides 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.
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