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2 edition of role of Ptc1 and Ptc2 in epidermal development, homeostasis and tumorigenesis found in the catalog.

role of Ptc1 and Ptc2 in epidermal development, homeostasis and tumorigenesis

Erica Nieuwenhuis

role of Ptc1 and Ptc2 in epidermal development, homeostasis and tumorigenesis

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Published .
Written in English


About the Edition

Hedgehog signaling plays a crucial role in the development and patterning of various tissues in vertebrates and invertebrates. In vertebrates, Patched1 (Ptc1) and Patched2 ( Ptc2) encode the receptors for the secreted signaling molecule, Shh. Ptc normally acts as a negative regulator of the Shh signaling pathway. When Shh is available to interact with Ptc, the pathway is activated resulting in the expression of target genes such as Ptc1 and Gli1. Interestingly, Ptc genes are expressed in a complimentary expression pattern in developing skin suggesting that they might possess distinct functions. Ptc1 has been shown to be a tumor suppressor but the role of Ptc1 in skin development has not been elucidated. Furthermore, the role of Ptc2 in development and tumorigenesis has not been determined. Ptc1, Ptc2 and Ptc1;Ptc2 mutants have been generated and analyzed to determine the unique and overlapping functions of Ptc1 and Ptc2. I have shown that Ptc2 is dispensable for embryogenesis, viability and reproduction, but required for adult epidermal homeostasis. Normal hair follicles could develop in the absence of Ptc1, but adults lacking normal Ptc1 function displayed epidermal hyperplasia and late-onset skin tumors. In Ptc1;Ptc2 double mutants epidermal development was greatly compromised. These mutants lacked hair follicles and a stratified epidermis, revealing the overlapping functions of Ptc genes. My data also unveiled that normal Ptc function is required in regulation of the epidermal progenitor cell population and uncovered c-myc as a novel target of Shh signaling in the adult epidermis. In conclusion, my study demonstrated the unique as well as overlapping roles of Ptc genes in epidermal development, homeostasis and tumorigenesis.

Edition Notes

Statementby Erica Nieuwenhuis.
The Physical Object
Paginationxiv, 232 leaves.
Number of Pages232
ID Numbers
Open LibraryOL19758098M
ISBN 109780494158524

  1) maintain homeostasis 2) protects skin from harmful substances (microorganisms) from entering body 3) retards water loss by diffusion from deeper tissues 4) helps regulate body temperature 5) houses sensory receptors 6) synthesizes various chemicals (Vitamin D) 7) contains immune system cells 8) excretes small quantities of waste. The Hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. In this review I discuss the role of Hedgehog signaling in the development, postnatal maintenance, and carcinogenesis of the gastrointestinal tract. Three mammalian hedgehog genes, sonic hedgehog (Shh.


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role of Ptc1 and Ptc2 in epidermal development, homeostasis and tumorigenesis by Erica Nieuwenhuis Download PDF EPUB FB2

Ptc2 displays overlapping expression with Shh in the epidermal compartment of the developing hair follicles, where Ptc1 and Ptc2 show a mostly nonoverlapping expression pattern, suggesting that Ptc2 might play a unique role during embryonic hair follicle by: Ptc2 displays overlapping expression with Shh in the epidermal compartment of the developing hair follicles, where Ptc1 and Ptc2 show a mostly nonoverlapping expression pattern, suggesting that Ptc2 might play a unique role during embryonic hair follicle development.

Mammalian haired skin is composed of a pilosebaceous unit that contains a hair follicle (HF) and its surrounding interfollicular epidermis (IFE) (see the figure, part a).

Stem cells (SCs) that are present in the skin ensure the continual turnover of the skin epidermis during tissue homeostasis and by: In the Ptc1 Δloop2-EGFP electroporated tissue, the endogenous mRNA levels of Ptc1, Ptc2 and Hip1, which are transcriptional targets of Shh signalling (Chuang and McMahon, ;Goodrich et al.

Why loss of Ptc1, but not Sufu, in the epidermis induces BCC formation is unclear. functions during skin development and tumorigenesis. p53 and G 2 /M checkpoints are characteristic of Cited by:   Ptc1 mes/mes mice develop epidermal hyperplasia postnatally, while embryonic hair follicle and epidermal development are not affected suggesting that the role of Ptc1 as a regulator of epidermal homeostasis or maintenance is required after by: Epidermal Homeostasis: The Role of the Growth Hormone and Insulin-Like Growth Factor Systems Article Literature Review (PDF Available) in Endocrine Reviews 24(6) January with.

Patched 1 and Patched 2 Redundancy Has a Key Role in Regulating Epidermal Differentiation analyses of zebrafish ptc1;ptc2 double mutants have indicated an increase in the level of Hh target W.

Nien, et 7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis. Development, Cited by: The epidermal growth factor receptor (EGFR) is activated by many ligands and belongs to a family of tyrosine kinase receptors, including ErbB2, ErbB3, and by: Roles of p63 in Epidermal Development and Tumorigenesis Jeng-Yuan Yao, Jan-Kan Chen Epidermis is composed mainly of keratinocytes and is the major barrier of human body.

The development and maintenance of normal epithelial structures and functions require the transcription factor pCited by: The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis.

Expression of Shh, Ptc1, and Ptc2 in pituitary adenomas. Colocalization of Shh and ACTH (A), Ptc2 and ACTH (B), Ptc2 and GH (C), and Ptc2 and prolactin (D) in the normal human pituitary gland.

The epidermis undergoes a constant turnover and distinct stem cells (SCs) are responsible for the homeostasis of the different epidermal compartments. Deregulation of the signaling pathways controlling the balance between renewal and differentiation often leads to cancer formation.

Mutations of p63 gene cause epidermal abnormalities characterized by ectodermal dysplasia. Recent reports have indicated that p63 plays important role in tumorigenesis as well.

However, the relative importance of TAp63 and ΔNp63 in epidermal development and tumorigenesis re-mains mostly unclear and awaits further by: Introduction 8 8 The pituitary gland and pituitary tumors The pituitary gland 11 Regulation of corticotroph cells by CRH 11 Pituitary tumors 12 16 Sonic hedgehog signal transduction pathway – an overview 18 Sonic hedgehog signaling pathway in human disease 20 Shh signaling in pituitary gland development self-renewal, dependent on stem cells residing in the epidermis, has to be assured.

These stem cells have a crucial role in maintaining epidermal homeostasis, hair regeneration and wound healing (Fuchs and Nowak, ). Figure 1 ǀ Skin morphology. Cross-section through mammalian skin. The existence of a sensory system for water flux or environmental humidity as a part of epidermal permeability barrier homeostasis has been suggested (Grubauer et al., ; Denda et al., a), and our results suggest that TRPV4 might be this sensor.

Further work is needed to understand the role of TRPV4 in epidermal barrier by: Patching the gaps in Hedgehog signalling.

ATOH1 targets in tumor cells involved in development and tumorigenesis. Among these targets specific to metastatic tumors, there was an enrichment in.

The Patched 1 (Ptch1) receptor has a pivotal role in inhibiting the activity of the Hedgehog (Hh) pathway and is therefore critical in preventing the onset of many human developmental disorders and tumor formation.

However, the functional role of the mammalian Ptch2 paralogue remains elusive, particularly the extent to which it contributes to regulating the spatial and temporal activity of Hh Cited by: known about the role of Ptc2 in development.

We have previously identified the mouse Ptc2 gene and shown that it displays over-lapping expression with Shh during epidermal development in mouse embryos (46). Mouse Ptc2 is located at mouse chromo-some 4C7-D1 (23), which is syntenic to human chromosome 1p, where multiple tumor suppressor genes have been.

One potential mechanism for deregulated Hh signaling to induce tumorigenesis is through this influence on cell cycle control. Hh signaling plays a conserved developmental role in controlling proliferation and patterning of the lung, 61,epidermal appendages, 3, 94, 99 muscle progenitors, 59,foregutand brain.

In adult animals, Hh signals are additionally required for Cited by: 1. Hedgehog signaling does play a role at later stages in development however.

Although no Shh is expressed during pancreatic development, Ihh and Ptc1 are expressed in the pancreas as detected by RT-PCR from E onwards, but their expression has Cited by:   The Gli proteins are critical components of multiple processes in development, homeostasis and disease, including neurogenesis and tumorigenesis.

However, it is unclear how the Gli code, the sum of their combinatorial positive and negative functions, dictates cell fate and behavior. Using an antisense approach to knockdown gene function in vivo, we find that each of the three Gli Cited by:   Cullin-RING Ligases (CRLs) are the largest family of E3 ubiquitin ligases, accounting for approximately 20% of proteins degraded by proteasome.

In this review, we discuss the role of CRLs in stem cell homeostasis, self-renewal, and differentiation and expound their ubiquitination : Lin Fu, Chun-Ping Cui, Lingqiang Zhang. In mammals, Shh signalling is involved with two Ptc receptors (Ptc1 and Ptc2) and at least three Gli proteins (Gli-1, Gli-2 and Gli-3) (Goetz et al., ).

The roles of Shh signalling in the mammal skin have been investigated previously, especially its important activity in controlling the growth of hair follicle and hair follicle by: HH proteins control cell growth, survival, and differentiation in a cell type-specific manner and by different mechanisms.

HH signaling directly regulates proliferation of cerebellar granule precursors and epidermal basal stem cells [9, 10] and indirectly supports other cell types by stimulating angiogenesis [11, 12].Functional heterozygosity for PTC1 is the cause of Gorlin's syndrome Cited by: PTC, BCNS, PTC1, PTCH, NBCCS: Location: 9q Summary: This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway.

Hedgehog signaling is important in embryonic development and tumorigenesis. A role for menin as a general co-regulator of transcription involved in epigenetic changes on histone proteins has emerged during the last decade (see “epigenetics”).

Alterations in the MEN1 gene play a limited role in sporadic pituitary tumorigenesis, and Cited by: 4. Xenograft mouse tumor study further demonstrates the essential role of EGFR in tumorigenesis of Cr(VI)-transformed cells.

In summary, the present study suggests that ligand-dependent constitutive activation of EGFR causes reduced ROS generation and increased antioxidant expression, leading to development of apoptosis resistance, contributing to.

Merkel cells (MCs) are located in the touch-sensitive area of the epidermis and mediate mechanotransduction in the skin. Whether MCs originate from embryonic epidermal or neural crest progenitors has been a matter of intense controversy since their discovery > yr ago.

In addition, how MCs are maintained during adulthood is currently unknown. Results Gli2 function is essential for hair follicle development. To identify the Gli transcription factors that mediate Shh responses during hair follicle development, we examined the skin phenotypes ofGli2 and Gli3 mutant mice.

Similar to wild-type skin, epithelial placodes form around embryonic day (E) inShh −/−, Gli2 −/−, andGli3 −/− skin (Fig.1A–D).Cited by: The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis.

Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known Cited by: Function.

PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in gene functions as a tumor PTCH1 gene product, is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgehog binds PTCH1, Aliases: PTCH1, BCNS, HPE7, NBCCS, PTC.

Hh signaling, first identified by its developmental role in Drosophila melanogaster, is an evolutionary conserved signaling pathway that is now known to have additional important roles in tissue homeostasis as well as tumorigenesis [1,2,3,4].In the late s, the field of embryonic development had no dogma to explain how the relatively simple body plan of drosophila embryos gave rise to the Cited by: Dissecting the Roles of Gli Activator and Repressor Functions during Epidermal Development and Disease.

Authors; Authors and affiliations Conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration. Tabin CJ. Ptc1 and Ptc2 transcripts provide distinct readouts of Hedgehog signaling. Protons dissociated from organic acids in cells are partly buffered.

If not, they are transported to the extracellular fluid through the plasma membrane and buffered in circulation or excreted in urine and expiration gas.

Several transporters including monocarboxylate transporters and Na + /H + exchanger play an important role in uptake and output of protons across plasma membranes in cells of Cited by: 9q microdeletion The PTCH1 gene is located in a region of chromosome 9 that is deleted in people with a 9q microdeletion.

As a result of this deletion, affected individuals are missing one copy of the PTCH1 gene in each cell. Despite its importance in skin development and tumorigenesis, little is known about the molecular regulation of Gli2. Increased expression of regulators of epidermal homeostasis, c-Myc and p63, was also observed in Ptc1(mes/mes) adult skin.

suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping. Thyroid cancer is the most common endocrine malignancy and its global incidence rates are rapidly increasing. Although the mortality of thyroid cancer is relatively low, its rate of recurrence or persistence is relatively high, contributing to incurability and morbidity of the disease.

Thyroid cancer is mainly treated by surgery and radioiodine remnant ablation, which is effective only for non Cited by: Cells within the adult vasculature were originally considered to be terminally differentiated.

Although vascular integrity underpins normal tissue physiology, vascular plasticity, including new vessel formation (vasculogenesis) and sprouting (angiogenesis) contributes to both healthy tissue repair and also disease development, highlighted by its importance in atherogenesis and tumorigenesis.

1 Cited by:. Given ihh expression in mutant cartilages, we next assayed for evidence of Hh signaling, which should be apparent in the expression of ptc1 and ptc2 (Goodrich et al., ; Lewis et al., ).

In wild-type 5 dpf ceratohyals, ptc1 and ptc2 expression was relatively high in perichondrium and low in chondrocytes (Fig. 9E and G).Every day your epidermis normally sheds dead skin cells. What is the first step in the process by which epidermal cells are replaced? Basal cells in the stratum germinativum divide, adding in new daughter cells and pushing the cells above upward through the layers.you Function Is Required for Hedgehog Signaling.

In wild-type zebrafish embryos, the dorsal and ventral portions of each myotome converge at a point where the horizontal myoseptum forms, giving the somites their characteristic chevron shape (Figure 1A).In contrast, you mutants lacked the horizontal myoseptum and exhibit the U-shaped morphology that defines mutants of the you class (Figure 1B; []).Cited by: