Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes

BACKGROUND: Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating from this level of the neuraxis are important for the development of the ophthalmic placode. RESULTS: Here, we provide the first evidence that both the ophthalmic and maxillomandibular placodes form under the influence of isthmic Wnt and FGF signals. Activated Wnt signals direct development of the Pax3 expressing ophthalmic placodal field and induce premature differentiation of both the ophthalmic and the maxillomandibular placodes. Similarly, overexpression of Fgf8 directs premature differentiation of the trigeminal placodes. Wnt signals require FGF receptor activity to initiate Pax3 expression and, subsequently, the expression of neural markers, such as Brn3a, within the cranial ectoderm. Furthermore, fibroblast growth factor signaling via the mitogen activated protein kinase pathway is required to maintain early neuronal differentiation within the trigeminal placodes. CONCLUSION: We demonstrate the identity of inductive signals that are necessary for trigeminal ganglion formation. This is the first report that describes how isthmic derived Wnt signals act in concert with fibroblast growth factor signaling. Together, both are necessary and sufficient for the establishment and differentiation of the ophthalmic and maxillomandibular placodes and, consequently, the trigeminal ganglion

Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes

<p>Abstract</p> <p>Background</p> <p>Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating from this level of the neuraxis are important for the development of the ophthalmic placode.</p> <p>Results</p> <p>Here, we provide the first evidence that both the ophthalmic and maxillomandibular placodes form under the influence of isthmic Wnt and FGF signals. Activated Wnt signals direct development of the <it>Pax3 </it>expressing ophthalmic placodal field and induce premature differentiation of both the ophthalmic and the maxillomandibular placodes. Similarly, overexpression of <it>Fgf8 </it>directs premature differentiation of the trigeminal placodes. Wnt signals require FGF receptor activity to initiate <it>Pax3 </it>expression and, subsequently, the expression of neural markers, such as <it>Brn3a</it>, within the cranial ectoderm. Furthermore, fibroblast growth factor signaling via the mitogen activated protein kinase pathway is required to maintain early neuronal differentiation within the trigeminal placodes.</p> <p>Conclusion</p> <p>We demonstrate the identity of inductive signals that are necessary for trigeminal ganglion formation. This is the first report that describes how isthmic derived Wnt signals act in concert with fibroblast growth factor signaling. Together, both are necessary and sufficient for the establishment and differentiation of the ophthalmic and maxillomandibular placodes and, consequently, the trigeminal ganglion.</p

WLS Retrograde Transport to the Endoplasmic Reticulum during Wnt Secretion

SummaryWnts are transported to the cell surface by the integral membrane protein WLS (also known as Wntless, Evi, and GPR177). Previous studies of WLS trafficking have emphasized WLS movement from the Golgi to the plasma membrane (PM) and then back to the Golgi via retromer-mediated endocytic recycling. We find that endogenous WLS binds Wnts in the endoplasmic reticulum (ER), cycles to the PM, and then returns to the ER through the Golgi. We identify an ER-targeting sequence at the carboxyl terminus of native WLS that is critical for ER retrograde recycling and contributes to Wnt secretory function. Golgi-to-ER recycling of WLS requires the COPI regulator ARF as well as ERGIC2, an ER-Golgi intermediate compartment protein that is also required for the retrograde trafficking of the KDEL receptor and certain toxins. ERGIC2 is required for efficient Wnt secretion. ER retrieval is an integral part of the WLS transport cycle

Changing-look Active Galactic Nuclei from the Dark Energy Spectroscopic Instrument. I. Sample from the Early Data

Changing-look active galactic nuclei (CL AGNs) can be generally confirmed by the emergence (turn-on) or disappearance (turn-off) of broad emission lines (BELs), associated with a transient timescale (about 100 ∼ 5000 days) that is much shorter than predicted by traditional accretion disk models. We carry out a systematic CL AGN search by crossmatching the spectra coming from the Dark Energy Spectroscopic Instrument and the Sloan Digital Sky Survey. Following previous studies, we identify CL AGNs based on Hα, Hβ, and Mg ii at z ≤ 0.75 and Mg ii, C iii], and C iv at z > 0.75. We present 56 CL AGNs based on visual inspection and three selection criteria, including 2 Hα, 34 Hβ, 9 Mg ii, 18 C iii], and 1 C iv CL AGN. Eight cases show simultaneous appearances/disappearances of two BELs. We also present 44 CL AGN candidates with significant flux variation of BELs, but remaining strong broad components. In the confirmed CL AGNs, 10 cases show additional CL candidate features for different lines. In this paper, we find: (1) a 24:32 ratio of turn-on to turn-off CL AGNs; (2) an upper-limit transition timescale ranging from 330 to 5762 days in the rest frame; and (3) the majority of CL AGNs follow the bluer-when-brighter trend. Our results greatly increase the current CL census (∼30%) and would be conducive to exploring the underlying physical mechanism

Changing-look Active Galactic Nuclei from the Dark Energy Spectroscopic Instrument. I. Sample from the Early Data

Changing-look active galactic nuclei (CL AGNs) can be generally confirmed by the emergence (turn-on) or disappearance (turn-off) of broad emission lines (BELs), associated with a transient timescale (about 100 ∼ 5000 days) that is much shorter than predicted by traditional accretion disk models. We carry out a systematic CL AGN search by crossmatching the spectra coming from the Dark Energy Spectroscopic Instrument and the Sloan Digital Sky Survey. Following previous studies, we identify CL AGNs based on Hα, Hβ, and Mg ii at z ≤ 0.75 and Mg ii, C iii], and C iv at z > 0.75. We present 56 CL AGNs based on visual inspection and three selection criteria, including 2 Hα, 34 Hβ, 9 Mg ii, 18 C iii], and 1 C iv CL AGN. Eight cases show simultaneous appearances/disappearances of two BELs. We also present 44 CL AGN candidates with significant flux variation of BELs, but remaining strong broad components. In the confirmed CL AGNs, 10 cases show additional CL candidate features for different lines. In this paper, we find: (1) a 24:32 ratio of turn-on to turn-off CL AGNs; (2) an upper-limit transition timescale ranging from 330 to 5762 days in the rest frame; and (3) the majority of CL AGNs follow the bluer-when-brighter trend. Our results greatly increase the current CL census (∼30%) and would be conducive to exploring the underlying physical mechanism

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Neural tube derived Wnt signals cooperate with FGF signaling in the formation and differentiation of the trigeminal placodes

Abstract Background Neurogenic placodes are focal thickenings of the embryonic ectoderm that form in the vertebrate head. It is within these structures that the precursors of the majority of the sensory neurons of the cranial ganglia are specified. The trigeminal placodes, the ophthalmic and maxillomandibular, form close to the midbrain-hindbrain boundary and many lines of evidence have shown that signals emanating from this level of the neuraxis are important for the development of the ophthalmic placode. Results Here, we provide the first evidence that both the ophthalmic and maxillomandibular placodes form under the influence of isthmic Wnt and FGF signals. Activated Wnt signals direct development of the Pax3 expressing ophthalmic placodal field and induce premature differentiation of both the ophthalmic and the maxillomandibular placodes. Similarly, overexpression of Fgf8 directs premature differentiation of the trigeminal placodes. Wnt signals require FGF receptor activity to initiate Pax3 expression and, subsequently, the expression of neural markers, such as Brn3a, within the cranial ectoderm. Furthermore, fibroblast growth factor signaling via the mitogen activated protein kinase pathway is required to maintain early neuronal differentiation within the trigeminal placodes. Conclusion We demonstrate the identity of inductive signals that are necessary for trigeminal ganglion formation. This is the first report that describes how isthmic derived Wnt signals act in concert with fibroblast growth factor signaling. Together, both are necessary and sufficient for the establishment and differentiation of the ophthalmic and maxillomandibular placodes and, consequently, the trigeminal ganglion.</p

How cognitive engagement fluctuates during a team-based learning session and how it predicts academic achievement

The objective of the paper is to report findings of two studies that attempted to find answers to the following questions: (1) What are the levels of cognitive engagement in TBL? (2) Are there differences between students who were more exposed to TBL than students who were less exposed to TBL? (3) To which extent does cognitive engagement fluctuate as a function of the different activities involved in TBL? And (4) How do cognitive engagement scores collected over time correlate with each other and with academic achievement? The studies were conducted with Year-1 and -2 medical students enrolled in a TBL curriculum (N = 175, 62 female). In both studies, six measurements of cognitive engagement were taken during the distinct TBL activities (preparation phase, individual/team readiness assurance test, burning questions, and application exercises). Data were analysed by means of one-way repeated-measures ANOVAs and path modelling. The results of the repeated-measures ANOVA revealed that cognitive engagement systematically fluctuated as a function of the distinct TBL activities. In addition, Year-1 students reported significantly higher levels of cognitive engagement compared to Year-2 students. Finally, cognitive engagement was a significant predictor of performance (β = .35). The studies presented in this paper are a first attempt to relate the different activities undertaken in TBL with the extent to which they arouse cognitive engagement with the task at hand. Implications of these findings for TBL are discussed