1 Developmental roles and clinical significance of Hedgehog signaling

McMahon, Andrew P.; Ingham, Philip W.; Tabin, Clifford J.

doi:10.1016/s0070-2153(03)53002-2

Cited by 833 publications

(704 citation statements)

References 593 publications

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“…It is involved in numerous key developmental events during embryogenesis, including left-right axis establishment, dorsoventral patterning of the neural tube, endoderm development, limb and craniofacial development, brain and pituitary development, among others (reviewed in Ingham and McMahon, 2001;McMahon et al, 2003;Roessler and Muenke, 2003, and references therein). The Shh signaling pathway is also involved in many human diseases, particularly holoprosencephaly and cancer (reviewed in Mullor et al, 2002;Roessler and Muenke, 2003).…”

Section: The Shh Pathwaymentioning

confidence: 99%

“…Through a series of steps that are currently not entirely understood, Smo activation leads to conversion of members of the Gli family of transcription factors from repressors to transcriptional activators and to activation of downstream gene expression. One of the downstream target genes of Shh signaling is Ptch1, thus establishing a feedback regulatory loop (reviewed in Ingham and McMahon, 2001;McMahon et al, 2003).…”

Section: The Shh Pathwaymentioning

confidence: 99%

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Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

284

304

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The vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross-regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis.

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Section: The Shh Pathwaymentioning

confidence: 99%

Section: The Shh Pathwaymentioning

confidence: 99%

Development of the upper lip: Morphogenetic and molecular mechanisms

Jiang

Bush

Lidral

2005

Developmental Dynamics

284

304

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“…2 Recent studies also implicate these proteins in cell fate determination and self-renewal of the hematopoietic system, and sonic hedgehog (SHH) is one of the survival signals provided by follicular dendritic cells to prevent apoptosis in germinal center B cells. 3,4 SHH ligand interacts with a receptor complex composed of two proteins, patched (PTCH) and smoothened (SMO).…”

mentioning

confidence: 99%

Sonic hedgehog signaling proteins and ATP-binding cassette G2 are aberrantly expressed in diffuse large B-Cell lymphoma

et al. 2009

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Dysregulation of the sonic hedgehog (SHH) signaling pathway has been shown in several cancer types, but has not been explored in diffuse large B-cell lymphoma. We assessed 67 cases of diffuse large B-cell lymphoma for expression of SHH (ligand), GLI1, GLI2 and GLI3 (transcriptional effectors of SHH signaling), and the ATPbinding cassette (ABC)G2 (a downstream target of SHH signaling), using immunohistochemistry. For comparison, we assessed the expression levels of these proteins in 28 cases of follicular lymphoma, 5 chronic lymphocytic leukemia/small lymphocytic lymphoma, and 5 reactive lymph nodes. In diffuse large B-cell lymphoma, SHH was expressed in 61 of 67 (91%) cases, GLI1 in 62 of 67 (93%), GLI2 in 41 of 56 (73%), and GLI3 in 22 of 56 (39%). Expression of ABCG2 was detected in 52 of 55 (95%) cases and was high in 15 (27%) cases. SHH expression positively correlated with expression levels of ABCG2 (P ¼ 0.05). Patients with diffuse large Bcell lymphoma with high ABCG2 expression showed significantly shorter overall survival (P ¼ 0.031) and failurefree survival (P ¼ 0.029) compared with patients with tumors with low or no expression of ABCG2. Diffuse large B-cell lymphomas expressed SHH, and GLI1, GLI2, and GLI3 more frequently and more intensely than cases of follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. In conclusion, our data show that SHH signaling proteins and ABCG2 are aberrantly expressed in diffuse large B-cell lymphoma and that ABCG2 expression has prognostic implications. These findings also provide evidence that dysregulation of the SHH pathway may be involved in the pathogenesis of diffuse large B-cell lymphoma.

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“…Shh is involved in establishing lateral asymmetry, the anterior-posterior limb axis, and development of the central nervous system. Ihh is a master regulator of endochondral bone development [McMahon et al, 2003].…”

mentioning

confidence: 99%

Indian hedgehog: Its roles and regulation in endochondral bone development

Lai

Mitchell

2005

J of Cellular Biochemistry

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Normal endochondral bone development requires the coordination of chondrocyte proliferation and differentiation. Indian hedgehog (Ihh) is a morphogen produced by chondrocytes in the early stage of terminal differentiation and plays several key roles in this process. Ihh regulates growth of adjacent proliferative chondrocytes and can also regulate the rate of differentiation of chondrocytes indirectly through its stimulation of parathyroid hormonerelated protein (PTHrP). In this review, we focus on recent studies that have identified new functions of Ihh and how Ihh itself is being regulated.

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1 Developmental roles and clinical significance of Hedgehog signaling

Cited by 833 publications

References 593 publications

Development of the upper lip: Morphogenetic and molecular mechanisms

Development of the upper lip: Morphogenetic and molecular mechanisms

Sonic hedgehog signaling proteins and ATP-binding cassette G2 are aberrantly expressed in diffuse large B-Cell lymphoma

Indian hedgehog: Its roles and regulation in endochondral bone development

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