The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform

Deepak Srivastava - One of the best experts on this subject based on the ideXlab platform.

  • the neural crest enriched microrna mir 452 regulates epithelial mesenchymal signaling in the First Pharyngeal Arch
    Development, 2010
    Co-Authors: Neil T Sheehy, Kathryn N Ivey, Kimberly R Cordes, Mark P White, Deepak Srivastava
    Abstract:

    Neural crest cells (NCCs) are a subset of multipotent, migratory stem cells that populate a large number of tissues during development and are important for craniofacial and cardiac morphogenesis. Although microRNAs (miRNAs) have emerged as important regulators of development and disease, little is known about their role in NCC development. Here, we show that loss of miRNA biogenesis by NCC-specific disruption of murine Dicer results in embryos lacking craniofacial cartilaginous structures, cardiac outflow tract septation and thymic and dorsal root ganglia development. Dicer mutant embryos had reduced expression of Dlx2, a transcriptional regulator of Pharyngeal Arch development, in the First Pharyngeal Arch (PA1). miR-452 was enriched in NCCs, was sufficient to rescue Dlx2 expression in Dicer mutant Pharyngeal Arches, and regulated non-cell-autonomous signaling involving Wnt5a, Shh and Fgf8 that converged on Dlx2 regulation in PA1. Correspondingly, knockdown of miR-452 in vivo decreased Dlx2 expression in the mandibular component of PA1, leading to craniofacial defects. These results suggest that post-transcriptional regulation by miRNAs is required for differentiation of NCC-derived tissues and that miR-452 is involved in epithelial-mesenchymal signaling in the Pharyngeal Arch.

  • Sonic Hedgehog Is Essential for First Pharyngeal Arch Development
    Pediatric Research, 2006
    Co-Authors: Chihiro Yamagishi, Hiroyuki Yamagishi, Jun Maeda, Takatoshi Tsuchihashi, Kathryn Ivey, Deepak Srivastava
    Abstract:

    The secreted protein sonic hedgehog (Shh) is essential for normal development of many organs. Targeted disruption of Shh in mouse leads to near complete absence of craniofacial skeletal elements at birth, and mutation of SHH in human causes holoprosencephaly (HPE), frequently associated with defects of derivatives of Pharyngeal Arches. To investigate the role of Shh signaling in early Pharyngeal Arch development, we analyzed Shh mutant embryos using molecular markers and found that the First Pharyngeal Arch (PA1) was specifically hypoplastic and fused in the midline, and remaining Arches were well formed at embryonic day (E) 9.5. Molecular analyses using specific markers suggested that the growth of the maxillary Arch and proximal mandibular Arch was severely defective in Shh -null PA1, whereas the distal mandibular Arch was less affected. TUNEL assay revealed an increase in the number of apoptotic signals in PA1 of Shh mutant embryos. Ectodermal expression of fibroblast growth factor ( Fgf )-8, a cell survival factor for Pharyngeal Arch mesenchyme, was down-regulated in the PA1 of Shh mutants. Consistent with this observation, downstream transcriptional targets of Fgf8 signaling in neural crest–derived mesenchyme, including Barx1 , goosecoid , and Dlx2 , were also down-regulated in Shh -null PA1. These results demonstrate that epithelial-mesenchymal signaling and transcriptional events coordinated by Shh, partly via Fgf8, is essential for cell survival and tissue outgrowth of the developing PA1.

  • articles sonic hedgehog is essential for First Pharyngeal Arch development
    2006
    Co-Authors: Chihiro Yamagishi, Hiroyuki Yamagishi, Jun Maeda, Takatoshi Tsuchihashi, Kathryn N Ivey, Deepak Srivastava
    Abstract:

    The secreted protein sonic hedgehog (Shh) is essential for normal development of many organs. Targeted disruption of Shh in mouse leads to near complete absence of craniofacial skeletal elements at birth, and mutation of SHH in human causes holoprosen- cephaly (HPE), frequently associated with defects of derivatives of Pharyngeal Arches. To investigate the role of Shh signaling in early Pharyngeal Arch development, we analyzed Shh mutant embryos using molecular markers and found that the First Pharyngeal Arch (PA1) was specifically hypoplastic and fused in the midline, and remaining Arches were well formed at embryonic day (E) 9.5. Molecular analyses using specific markers suggested that the growth of the maxillary Arch and proximal mandibular Arch was severely defective in Shh-null PA1, whereas the distal mandibular Arch was less affected. TUNEL assay revealed an increase in the number of apoptotic signals in PA1 of Shh mutant embryos. Ectodermal expression of fibroblast growth factor (Fgf)-8, a cell survival factor for Pharyngeal Arch mesenchyme, was down- regulated in the PA1 of Shh mutants. Consistent with this obser- vation, downstream transcriptional targets of Fgf8 signaling in neural crest-derived mesenchyme, including Barx1, goosecoid, and Dlx2, were also down-regulated in Shh-null PA1. These results demonstrate that epithelial-mesenchymal signaling and transcriptional events coordinated by Shh, partly via Fgf8, is essential for cell survival and tissue outgrowth of the developing PA1. (Pediatr Res 59: 349-354, 2006)

Ramkumar Sambasivan - One of the best experts on this subject based on the ideXlab platform.

  • modulation of β catenin levels regulates cranial neural crest patterning and dispersal into First Pharyngeal Arch
    Developmental Dynamics, 2020
    Co-Authors: Alok Javali, Vairavan Lakshmanan, Dasaradhi Palakodeti, Ramkumar Sambasivan
    Abstract:

    BACKGROUND Vertebrate cranial neural crest cells (CNCCs) are multipotent, proximal to the source CNCC form the cranial ganglia. Distally, in the Pharyngeal Arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. RESULTS Here, we report that a novel β-catenin-dependent regulation of N-Cadherin levels may drive CNCC patterning. In mouse embryos, at the First Pharyngeal Arch axial level, membrane β-catenin levels correlate with the extent of N-cadherin-mediated adhesion and thus suggest the presence of collective and dispersed states of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for regulating N-cadherin levels and cell-cell adhesion. Similarly, in β-catenin gain-of-function mutant mouse embryos, CNCC fail to lower N-cadherin levels. This indicates a failure to reduce cell-cell adhesion, which may underlie the failure of mutant CNCC to populate First Pharyngeal Arch. CONCLUSION We suggest that β-catenin-mediated regulation of CNCC adhesion, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.

  • Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into First Pharyngeal Arch
    2019
    Co-Authors: Alok Javali, Vairavan Lakshmanan, Dasaradhi Palakodeti, Ramkumar Sambasivan
    Abstract:

    Abstract Vertebrate cranial neural crest cells (CNCC) are multipotent. Proximal to the source CNCC form the cranial ganglia. Distally, in the Pharyngeal Arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. Here, we report that a novel β-catenin-controlled switch in the cell arrangement is critical in patterning CNCC. In mouse embryos, at the First Pharyngeal Arch axial level, membrane β-catenin levels correlate with the extent of cell-cell adhesion and thus, with a collective or a dispersed state of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for the collective-to-dispersed switch. Similarly, in β-catenin gain of function mutant mouse embryos, CNCC fail to disperse, which may underlie their failure to populate First Pharyngeal Arch. Thus, we show that β-catenin-mediated regulation of CNCC tissue Architecture, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments. Summary statement The report shows a crucial step in cranial neural crest patterning. Neural crest cells invading the Pharyngeal Arches transition from a collective to dispersed state. This transition in cell arrangement is dependent on membrane β-catenin levels.

Eglantine Heude - One of the best experts on this subject based on the ideXlab platform.

  • Probing the origin of matching functional jaws: roles of Dlx5/6 in cranial neural crest cells
    Nature Publishing Group, 2018
    Co-Authors: Miki Shimizu, Eglantine Heude, Nicolas Narboux-nême, Yorick Gitton, Camille De Lombares, Anastasia Fontaine, Gladys Alfama, Taro Kitazawa, Yumiko Kawamura, Lindsey Marshall
    Abstract:

    Abstract Gnathostome jaws derive from the First Pharyngeal Arch (PA1), a complex structure constituted by Neural Crest Cells (NCCs), mesodermal, ectodermal and endodermal cells. Here, to determine the regionalized morphogenetic impact of Dlx5/6 expression, we specifically target their inactivation or overexpression to NCCs. NCC-specific Dlx5/6 inactivation (NCC ∆Dlx5/6 ) generates severely hypomorphic lower jaws that present typical maxillary traits. Therefore, differently from Dlx5/6 null-embryos, the upper and the lower jaws of NCC ∆Dlx5/6 mice present a different size. Reciprocally, forced Dlx5 expression in maxillary NCCs provokes the appearance of distinct mandibular characters in the upper jaw. We conclude that: (1) Dlx5/6 activation in NCCs invariably determines lower jaw identity; (2) the morphogenetic processes that generate functional matching jaws depend on the harmonization of Dlx5/6 expression in NCCs and in distinct ectodermal territories. The co-evolution of synergistic opposing jaws requires the coordination of distinct regulatory pathways involving the same transcription factors in distant embryonic territories

  • masticatory muscle defects in hemifacial microsomia a new embryological concept
    American Journal of Medical Genetics Part A, 2011
    Co-Authors: Eglantine Heude, Isabelle Rivals, Gérard Couly, Giovanni Levi
    Abstract:

    First Arch syndromes correspond to a wide spectrum of human latero-facial congenital anomalies affecting cranial neural crest cells (CNCCs) derivatives of the First Pharyngeal Arch (PA1). The abnormal traits display variable quantitative expression and are often unilateral. Mandibular skeletal defects are invariably accompanied by hypoplasia or agenesis of masticatory muscles, but no explanation has been proposed for this association. Indeed, during embryonic development, CNCCs give only rise to skeletal components of the head while muscles derive from cephalic myogenic mesodermal cells (CMMCs). Recent studies on animal models have shown that communication between CNCCs and CMMCs is essential for the development of masticatory muscles: genetic lesions affecting only CNCCs can prevent muscularization of the jaws. To evaluate the involvement of CNCC/CMMC interactions in human craniofacial development, we performed a quantitative analysis of masticatory muscle and mandibular bone volumes on craniofacial CT-scans from 8 children, ages 3 months to 16 years, affected by hemifacial microsomia. We found that: (1) in seven patients the masseter muscle is absent in the affected side; (2) the absence of masseter is correlated neither with the age of the patients nor with the volume and shape of the affected ramus; and (3) in all cases the pterygoid and the temporal muscles are either reduced or absent. Our findings suggest that an early developmental event is the origin of the muscular defects in these patients. We propose that the hypoplasia or agenesis of masticatory muscles derives from a defect in the CNCCs/CMMCs communication during early embryonic development. © 2011 Wiley-Liss, Inc.

  • an endothelin 1 switch specifies maxillomandibular identity
    Proceedings of the National Academy of Sciences of the United States of America, 2008
    Co-Authors: Takahiro Sato, Eglantine Heude, Giovanni Levi, Yumiko Kawamura, Yukiko Kurihara, Rieko Asai, Kazuo Tonami, Yasunobu Uchijima, Marc Ekker, Hiroki Kurihara
    Abstract:

    Articulated jaws are highly conserved structures characteristic of gnathostome evolution. Epithelial-mesenchymal interactions within the First Pharyngeal Arch (PA1) instruct cephalic neural crest cells (CNCCs) to form the different skeletal elements of the jaws. The endothelin-1 (Edn1)/endothelin receptor type-A (Ednra)→Dlx5/6→Hand2 signaling pathway is necessary for lower jaw formation. Here, we show that the Edn1 signaling is sufficient for the conversion of the maxillary Arch to mandibular identity. Constitutive activation of Ednra induced the transformation of upper jaw, maxillary, structures into lower jaw, mandibular, structures with duplicated Meckel's cartilage and dermatocranial jaws constituted by 4 dentary bones. Misexpression of Hand2 in the Ednra domain caused a similar transformation. Skeletal transformations are accompanied by neuromuscular remodeling. Ednra is expressed by most CNCCs, but its constitutive activation affects predominantly PA1. We conclude that after migration CNCCs are not all equivalent, suggesting that their specification occurs in sequential steps. Also, we show that, within PA1, CNCCs are competent to form both mandibular and maxillary structures and that an Edn1 switch is responsible for the choice of either morphogenetic program.

Leonard I Zon - One of the best experts on this subject based on the ideXlab platform.

  • neural crest development and craniofacial morphogenesis is coordinated by nitric oxide and histone acetylation
    Chemistry & Biology, 2014
    Co-Authors: Max L Dougherty, Michael Grimaldi, Yawei Kong, Eugene Curtin, Charles K Kaufman, Richard M White, Leonard I Zon
    Abstract:

    Cranial neural crest (CNC) cells are patterned and coalesce to facial prominences that undergo convergence and extension to generate the craniofacial form. We applied a chemical genetics approach to identify pathways that regulate craniofacial development during embryogenesis. Treatment with the nitric oxide synthase inhibitor 1-(2-[trifluoromethyl] phenyl) imidazole (TRIM) abrogated First Pharyngeal Arch structures and induced ectopic ceratobranchial formation. TRIM promoted a progenitor CNC fate and inhibited chondrogenic differentiation, which were mediated through impaired nitric oxide (NO) production without appreciable effect on global protein S-nitrosylation. Instead, TRIM perturbed hox gene patterning and caused histone hypoacetylation. Rescue of TRIM phenotype was achieved with overexpression of histone acetyltransferase kat6a, inhibition of histone deacetylase, and complementary NO. These studies demonstrate that NO signaling and histone acetylation are coordinated mechanisms that regulate CNC patterning, differentiation, and convergence during craniofacial morphogenesis.

Matthew J. Mason - One of the best experts on this subject based on the ideXlab platform.

  • early development of the malleus and incus in humans
    Journal of Anatomy, 2016
    Co-Authors: Charlotte Burford, Matthew J. Mason
    Abstract:

    It is widely accepted by developmental biologists that the malleus and incus of the mammalian middle ear are First Pharyngeal Arch derivatives, a contention based originally on classical embryology that has now been backed up by molecular evidence from rodent models. However, it has been claimed in several studies of human ossicular development that the manubrium of the malleus and long process of the incus are actually derived from the second Arch. This 'dual-Arch' interpretation is commonly presented in otolaryngology textbooks, and it has been used by clinicians to explain the aetiology of certain congenital abnormalities of the human middle ear. In order to re-examine the origins of the human malleus and incus, we made three-dimensional reconstructions of the Pharyngeal region of human embryos from 7 to 28 mm crown-rump length, based on serial histological sections from the Boyd Collection. We considered the positions of the developing ossicles relative to the Pharyngeal pouches and clefts, and the facial and chorda tympani nerves. Confirming observations from previous studies, the primary union between First Pharyngeal pouch and First cleft found in our youngest specimens was later lost, the external meatus developing rostroventral to this position. The mesenchyme of the First and second Arches in these early embryos seemed to be continuous, but the boundaries of the developing ossicles proved to be very hard to determine at this stage. When First distinguishable, the indications were that both the manubrium of the malleus and the long process of the incus were emerging within the First Pharyngeal Arch. We therefore conclude that the histological evidence, on balance, favours the 'classical' notion that the human malleus and incus are First-Arch structures. The embryological basis of congenital ossicular abnormalities should be reconsidered in this light.