Cloning of vertebrate <i>Protogenin</i> (<i>Prtg</i>) and comparative expression analysis during axis elongation

Vesque, Christine; Anselme, Isabelle; Couvé, Elisabeth; Charnay, Patrick; Schneider‐Maunoury, Sylvie

doi:10.1002/dvdy.20898

Cited by 15 publications

(20 citation statements)

References 31 publications

(30 reference statements)

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“…In the chick spinal cord, Prtg expression is inversely correlated with Ascl1 expression, similar to what we have found in the retina (48). Prtg is a member of the DCC/Neogenin family (49,50) and contains four Ig and five fibronectin III domains in the extracellular domain. Ligands for Prtg have not been identified, and the intracellular domain does not share significant homology with the other four members of this family (DCC/Neogenin/Punc/Nope).…”

Section: Discussionsupporting

confidence: 85%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

197

189

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Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.heterochronic | progenitor competence

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Section: Discussionsupporting

confidence: 85%

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Torre

Georgi²,

Reh

2013

Proc. Natl. Acad. Sci. U.S.A.

197

189

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“…The extracellular domain of Punc has the highest identity (43.8%) with that of Prtg. 25 The interaction between Prtg and Radil is mediated through the cytoplasmic domain of Prtg, as cytosolic domain-deleted Prtg (PrtgΔc) cannot associate with Radil (Figure 5c, lane 3).…”

Section: Resultsmentioning

confidence: 99%

Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5β1-integrin

Wang¹,

Jian-xin²,

Wong³

et al. 2013

Cell Death Dis

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The bones and connective tissues of the murine jaws and skull are partly derived from cephalic neural crest cells (CNCCs). Here, we report that mice deficient of protogenin (Prtg) protein, an immunoglobulin domain-containing receptor expressed in the developing nervous system, have impairments of the palatine and skull. Data from lineage tracing experiments, expression patterns of neural crest cell (NCC) marker genes and detection of apoptotic cells indicate that the malformation of bones in Prtg-deficient mice is due to increased apoptosis of rostral CNCCs (R-CNCCs). Using a yeast two-hybrid screening, we found that Prtg interacts with Radil, a protein previously shown to affect the migration and survival of NCCs in zebrafish with unknown mechanism. Overexpression of Prtg induces translocation of Radil from cytoplasm to cell membrane in cultured AD293 cells. In addition, overexpression of Prtg and Radil activates α5β1-integrins to high-affinity conformational forms, which is further enhanced by the addition of Prtg ligand ERdj3 into cultured cells. Blockage of Radil by RNA interference abolishes the effect of ERdj3 and Prtg on the α5β1-integrin, suggesting that Radil acts downstream of Prtg. Prtg-deficient R-CNCCs display fewer activated α5β1-integrins in embryos, and these cells show reduced migratory ability in in vitro transwell assay. These results suggest that the inside-out activation of the α5β1-integrin mediated by ERdj3/Prtg/Radil signaling is crucial for proper functions of R-CNCCs, and the deficiency of this pathway causes premature apoptosis of a subset of R-CNCCs and malformation of craniofacial structures.

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“…Protogenin (PRTG) is a recently identified IgSF member in chick and mouse embryos (Toyoda et al, 2005;Vesque et al, 2006) and belongs to the DCC/neogenin subclass of IgSF. Unlike DCC and neogenin, the expression of which starts around midgestation (Gad et al, 1997), the expression of PRTG mRNA initiates immediately after gastrulation in mouse embryos and undergoes a sharp downregulation after embryonic day 10 (E10) (Vesque et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike DCC and neogenin, the expression of which starts around midgestation (Gad et al, 1997), the expression of PRTG mRNA initiates immediately after gastrulation in mouse embryos and undergoes a sharp downregulation after embryonic day 10 (E10) (Vesque et al, 2006). Recently, Wigg et al (2008) identified a possible association between PRTG and human attention deficit hyperactivity disorder.…”

Section: Introductionmentioning

confidence: 99%

Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Wong¹,

Wang

et al. 2010

J. Neurosci.

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Many Ig superfamily members are expressed in the developing nervous system, but the functions of these molecules during neurogenesis are not all clear. Here, we explore the expression and function of one of members of this superfamily, protogenin (PRTG), in the developing nervous system. Expression of PRTG protein is strong in the neural tube of mouse embryos between embryonic days 7.75 and 9.5 but disappears after embryonic day 10.5 when the neural progenitor marker nestin expresses prominently. Perturbation of PRTG activity in P19 embryonal carcinoma cells and in chick embryos, by either RNA interference or a dominant-negative PRTG mutant, increases neuronal differentiation. Using yeast two-hybrid screening and an in situ binding assay, we were able to identify ERdj3 (a stress-inducible endoplasmic reticulum DnaJ homolog) as a putative PRTG ligand. Addition of purified ERdj3 protein into the P19 differentiation assay reduced neurogenesis. This effect was blocked by addition of either a neutralizing antibody against PRTG or purified PRTG ectodomain protein, indicating that the effect of ERdj3 on neurogenesis is mediated through PRTG. Forced expression of ERdj3 in the chick neural tube also impairs neuronal differentiation. Together, these results suggest that expression of PRTG defines a stage between pluripotent epiblasts and committed neural progenitors, and its signaling plays a critical role in suppressing premature neuronal differentiation during early neural development.

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Cloning of vertebrate Protogenin (Prtg) and comparative expression analysis during axis elongation

Cited by 15 publications

References 31 publications

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Conserved microRNA pathway regulates developmental timing of retinal neurogenesis

Protogenin prevents premature apoptosis of rostral cephalic neural crest cells by activating the α5β1-integrin

Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

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