PAPC couples the Segmentation Clock to somite morphogenesis by regulating N-cadherin dependent adhesion

Vertebrate segmentation is characterized by the periodic formation of epithelial somites from the mesenchymal presomitic mesoderm (PSM). How the rhythmic signaling pulse delivered by the Segmentation Clock is translated into the periodic morphogenesis of somites remains poorly understood. Here, we focused on the role of Paraxial protocadherin (PAPC/Pcdh8) in this process. We show that in chicken and mouse embryos, PAPC expression is tightly regulated by the Clock and Wavefront system in the posterior PSM. We observed that PAPC exhibits a striking complementary pattern to N-Cadherin (CDH2), marking the interface of the future somite boundary in the anterior PSM. Gain and loss of function of PAPC in chicken embryos disrupt somite segmentation by altering the CDH2-dependent epithelialization of PSM cells. Our data suggest that clathrin-mediated endocytosis is increased in PAPC expressing cells, subsequently affecting CDH2 internalization in the anterior compartment of the future somite. This in turn generates a differential adhesion interface, allowing formation of the acellular fissure that defines the somite boundary. Thus periodic expression of PAPC downstream of the Segmentation Clock triggers rhythmic endocytosis of CDH2, allowing for segmental de-adhesion and individualization of somites.

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Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy geneDll3are associated with disruption of the segmentation clock within the presomitic mesoderm

Development ◽

10.1242/dev.129.7.1795 ◽

2002 ◽

Vol 129 (7) ◽

pp. 1795-1806 ◽

Cited By ~ 7

Author(s):

Sally L. Dunwoodie ◽

Melanie Clements ◽

Duncan B. Sparrow ◽

Xin Sa ◽

Ronald A. Conlon ◽

...

Keyword(s):

Gene Targeting ◽

Skeletal Dysplasia ◽

Null Allele ◽

Developmental Origins ◽

Loss Of Function ◽

Presomitic Mesoderm ◽

Phenotypic Analysis ◽

Segmentation Clock ◽

Skeletal Defects ◽

Somite Formation

A loss-of-function mutation in the mouse delta-like3 (Dll3) gene has been generated following gene targeting, and results in severe axial skeletal defects. These defects, which consist of highly disorganised vertebrae and costal defects, are similar to those associated with the Dll3-dependent pudgy mutant in mouse and with spondylocostal dysplasia (MIM 277300) in humans. This study demonstrates that Dll3neo and Dll3pu are functionally equivalent alleles with respect to the skeletal dysplasia, and we suggest that the three human DLL3 mutations associated with spondylocostal dysplasia are also functionally equivalent to the Dll3neo null allele. Our phenotypic analysis of Dll3neo/Dll3neo mutants shows that the developmental origins of the skeletal defects lie in delayed and irregular somite formation, which results in the perturbation of anteroposterior somite polarity. As the expression of Lfng, Hes1, Hes5 and Hey1 is disrupted in the presomitic mesoderm, we suggest that the somitic aberrations are founded in the disruption of the segmentation clock that intrinsically oscillates within presomitic mesoderm.

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Role of dpp signalling in prepattern formation of the dorsocentral mechanosensory organ in Drosophila melanogaster

Development ◽

10.1242/dev.125.21.4215 ◽

1998 ◽

Vol 125 (21) ◽

pp. 4215-4224 ◽

Cited By ~ 5

Author(s):

Y. Tomoyasu ◽

M. Nakamura ◽

N. Ueno

Keyword(s):

Imaginal Disc ◽

Cluster Formation ◽

Dorsal Side ◽

Wing Imaginal Disc ◽

Loss Of Function ◽

Expression Domain ◽

Anterior Compartment ◽

Posterior Side ◽

Proneural Cluster

A proneural cluster of dorsocentral bristles forms adjacent to the dorsal side of wg-expressing cells in the notum region of the wing imaginal disc. It has been shown that wg activity is required for these structures to form. However, the restriction of this proneural cluster to the dorsal posterior side of the wg expression domain in the anterior compartment of the wing imaginal disc has suggested that Wg signalling itself is insufficient to establish the dorsocentral proneural cluster. Some factor(s) from the posterior side must participate in this action in cooperation with Wg signalling. We have examined the role of Dpp signalling in dorsocentral bristle formation by either ectopically activating or conditionally reducing Dpp signalling. Ubiquitous activation of Dpp signalling in the notum region of the wing imaginal disc induced additional dorsocentral proneural cluster all along the dorsal side of the wg expression domain, and altered wg expression. Conditional loss-of-function of Dpp signalling during disc development resulted in the inhibition of dorsocentral proneural cluster formation and expansion of the wg expression domain. These results suggest that Dpp signalling has two indispensable roles in dorsocentral bristle formation: induction of the dorsocentral proneural cluster in cooperation with Wg signalling and restriction of the wg expression domain in the notum region of the wing imaginal disc.

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Localization of Intracisternal a Particle Antigens in Neoplastic Cells and Preimplantation Mouse Embryos

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003044 ◽

1980 ◽

Vol 38 ◽

pp. 696-697

Author(s):

Thomas T.F. Huang ◽

Patricia G. Calarco

Keyword(s):

Endoplasmic Reticulum ◽

Normal Development ◽

Mouse Embryos ◽

Neoplastic Cells ◽

Large Numbers ◽

Preimplantation Mouse Embryos ◽

Preimplantation Mouse ◽

Intracisternal A Particle ◽

Normal Feature

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.

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Challenges of Fear Conditioning Research in the Age of RDoC

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000303 ◽

2017 ◽

Vol 225 (3) ◽

pp. 189-199 ◽

Cited By ~ 5

Author(s):

Tina B. Lonsdorf ◽

Jan Richter

Keyword(s):

Fear Conditioning ◽

Clinical Diagnosis ◽

Research Domain Criteria ◽

Major Focus ◽

The Future ◽

Definition Of ◽

Methodological Considerations ◽

Research Domain

Abstract. As the criticism of the definition of the phenotype (i.e., clinical diagnosis) represents the major focus of the Research Domain Criteria (RDoC) initiative, it is somewhat surprising that discussions have not yet focused more on specific conceptual and procedural considerations of the suggested RDoC constructs, sub-constructs, and associated paradigms. We argue that we need more precise thinking as well as a conceptual and methodological discussion of RDoC domains and constructs, their interrelationships as well as their experimental operationalization and nomenclature. The present work is intended to start such a debate using fear conditioning as an example. Thereby, we aim to provide thought-provoking impulses on the role of fear conditioning in the age of RDoC as well as conceptual and methodological considerations and suggestions to guide RDoC-based fear conditioning research in the future.

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