Project description:Few 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 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 Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals, but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, pre-dating a complex nervous system. We used progenitors for anterior and posterior sensory placodes dissected from chick embryos HH5-7; these were either processed immediately or cultured for 5 hrs to hybridise to Affymetrix chick array. We aimed to identify genes that are co regualted with Pax6, a key regulator of lens and olfactory progenitor cells. Pax6 is normally present in anterior, but not posterior placode precursors, but upregulated in both after 5 hrs culture.
Project description:Few 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 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 Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals, but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, pre-dating a complex nervous system.
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
Project description:The first morphological evidence of the developing ear is a thickened disk of ectoderm known as the otic placode. However, signals for otogenesis are present even before the otic placode is physically apparent. Several inductive signals have been identified through candidate gene approaches, but there are still many gaps in the signaling cascade of otogenesis. Presently the candidate gene approach has largely exhausted known candidates. This project compares the pre-otic domain with a control region that is competent, but not specified to form otic placode. The purpose of this work is to identify genes that are differentially expressed in the pre-otic domain in order to generate a list of novel candidate genes for otic placode induction.
Project description:During development, dermal papilla precursor cells (DPPCs) initiate embryonic hair follicle (HF) formation with epidermal placode cells. Obtaining DPPCs with trichogenic ability is critical for human HF regeneration because dermal papilla cells (DPCs) rapidly loseDuring development, dermal papilla precursor cells (DPPCs) initiate embryonic hair follicle (HF) formation with epidermal placode cells. Obtaining DPPCs with trichogenic ability is critical for human HF regeneration because dermal papilla cells (DPCs) rapidly lose their trichogenic ability in culture. Here, we generated trichogenic DPPCs from human induced pluripotent stem cells (iPSCs) via neural crest stem cells (NCSCs), based on the developmental evidence at the hair placode stage. SDC1+CD133− cells showed signature DP gene expression, spontaneous sphere formation and represented intermediate population in the differentiation way from NCSCs to DPCs. hiPSC-derived DPPCs generated HF equivalents in vitro and reconstituted de novo human HFs in vivo combined with hiPSC-derived epithelial stem cells. Remarkably, trichogenic ability of DPPC was only proven in the specific time window, providing insights into the loss of trichogenicity in cultured DPC. Thus, this study provides an in vitro model for studying DPC development and biology.
Project description:Cranial placodes contribute to all sense organs and sensory ganglia in the vertebrate head. Despite their diversity they originate from a common pool of Six1/Eya2+ progenitors. In a molecular screen we identify new factors upstream of the Six1/Eya2 cassette and use these to dissect the transcriptional hierarchy that controls progenitor specification. We find that although two different tissues, the lateral head mesoderm and the prechordal mesendoderm, induce placode progenitors, both initiate a common transcriptional state, but over time gradually impart regional character. Thus, as cells acquire placode progenitor identify they pass through successive transcriptional states each identified by a distinct set of factors and controlled by different signalling pathways. Thus, we propose a new model for placode progenitor induction reminiscent of Waddington’s evocation-individuation model for neural induction.