https://www.ncbi.nlm.nih.gov/pubmed/20034104
Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and formation of tracheal cartilage.
Park J1,
Zhang JJ,
Moro A,
Kushida M,
Wegner M,
Kim PC.
Author information
Abstract
We report that Sonic Hedgehog (Shh) regulates both formation and patterning of tracheal cartilage by controlling the expression pattern and level of the chondrogenic gene, Sox9. In Shh(-/-) tracheo-esophageal tubes, Sox9 expression is transient and not restricted ventrally to the site of chondrogenesis, and is absent at the time of chondrogenesis, resulting in the failure of tracheal cartilage formation. Inhibition of Hedgehog signalling with cyclopamine in tracheal cultures prevents tracheal cartilage formation, while treatment of Shh(-/-) tracheal explant with exogenous Shh peptide rescues cartilage formation. Both exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh(-/-) tracheal culture, while promoting excessive cartilage development in wild-type trachea through induction of Sox9 expression. The ventral and segmented expression of Sox9 in tracheal primordia under Shh modulated by Bmp4 and Noggin thus determine where and when tracheal cartilage develops.
These results indicate that Shh signalling is a critical determinant in tracheal cartilage development.
5th most upregulated gene in non-Androgenetic Alopecia scalp:
https://patentimages.storage.googleapis.com/US20110021599A1/US20110021599A1-20110127-D00088.png
https://www.genecards.org/cgi-bin/carddisp.pl?gene=COMP
Cartilage Oligomeric Matrix Protein
Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment.
Vidal VP1,
Chaboissier MC,
Lützkendorf S,
Cotsarelis G,
Mill P,
Hui CC,
Ortonne N,
Ortonne JP,
Schedl A.
Author information
Abstract
BACKGROUND:
The mammalian hair represents an unparalleled model system to understand both developmental processes and stem cell biology. The hair follicle consists of several concentric epithelial sheaths with the outer root sheath (ORS) forming the outermost layer. Functionally, the ORS has been implicated in the migration of hair stem cells from the stem cell niche toward the hair bulb. However, factors required for the differentiation of this critical cell lineage remain to be identified. Here, we describe an unexpected role of the HMG-box-containing gene Sox9 in hair development.
RESULTS:
Sox9 expression can be first detected in the epithelial component of the hair placode but then becomes restricted to the outer root sheath (ORS) and the hair stem cell compartment (bulge).
Using tissue-specific inactivation of Sox9, we demonstrate that this gene serves a crucial role in hair differentiation and that skin deleted for Sox9 lacks external hair. Strikingly, the ORS acquires epidermal characteristics with ectopic expression of GATA3. Moreover, Sox9 knock hair show severe proliferative defects and the stem cell niche never forms. Finally, we show that Sox9 expression depends on sonic hedgehog (Shh) signaling and demonstrate overexpression in skin tumors in mouse and man.
CONCLUSIONS:
We conclude that although Sox9 is dispensable for hair induction, it directs differentiation of the ORS and is required for the formation of the hair stem cell compartment.
Our genetic analysis places Sox9 in a molecular cascade downstream of sonic hedgehog and suggests that this gene is involved in basal cell carcinoma.
From the gene differences comparision study at
http://sci-hub.tw/https://doi.org/10.1111/jdv.14278 at page 10,
it listed the following pathways as downregulated in Androgenetic Alopecia tissues:
Hedgehog signaling pathway
Progesterone-mediated oocyte maturation
Oocyte meiosis
SNARE interactions in vesicular transport
Phospholipase D signaling pathway
Maturity onset diabetes of the young
Synthesis and degradation of ketone bodies
Transcriptional misregulation in cancer
Basal cell carcinoma
Pathways in cancer
so the study said reduction of sox9, which is a downstream target gene of Hegdheog signalling = increases of GATA3 and etopic expression of it in parts of the hair follicle where it shouldn't even be expressed. so what is GATA3?:
https://www.researchgate.net/figure...A-3-is-induced-by-TCR-and-IL-4_fig4_263130756
= GATA3 is master regulator of Th2 cytokines and is:
GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells Umberto De Fanis,1 Francesca Mori,1 Rebecca J. Kurnat,1 Won Kyung Lee,1 Maria Bova,1 N. Franklin Adkinson,1 and Vincenzo Casolaro1 1Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell development and function. Consistently, studies in mice document their selective expression in Th1 and Th2 cells, respectively. In contrast, it is not clear whether these genes are regulated in human Th cells. Here we show that T-bet expression is polarized to a comparable degree in human and mouse Th-cell cultures, while only mouse GATA3 is subject to substantial regulation. This did not reflect differential skewing efficiency in human versus mouse cultures, as these contained similar frequencies of IFN-– and IL-4– producing cells.
However, GATA-3 was expressed at significantly higher levels in human IL-4–producing cells enriched via capture with monoclonal antibodies (mAbs) against the PGD2 receptor, CRTH2, the best selective Th2-cell surface marker to date. Along with increased IL-4 and GATA-3, CRTH2 Th cells isolated from Th2-skewed cultures or the circulating memory pool exhibited markedly decreased IFN- and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to polarizing signals that are sufficient to direct Th2-specific expression in mouse cells. This postulates the involvement of an additional level of complexity in the regulation of human GATA-3 expression and stresses the existence of nontrivial differences in the regulation of human versus mouse T-cell function. (Blood. 2007;109:4343-4350)
= GATA3 ups Th2, which in turn ups PGD2 to up CRTH2
Prostaglandin D2 enhances lipid accumulation through suppression of lipolysis via DP2 (CRTH2) receptors in adipocytes.
Wakai E1,
Aritake K2,
Urade Y3,
Fujimori K4.
Author information
Abstract
Prostaglandin (PG) D2 enhanced lipid accumulation in adipocytes. However, its molecular mechanism remains unclear.
In this study, we investigated the regulatory mechanisms of PGD2-elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD2 receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD2-elevated intracellular triglyceride level.
While, a DP2R agonist, 15R-15-methyl PGD2(15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level. In addition, the forskolin-mediated increase of cAMP-dependent protein kinase A (PKA) activity and phosphorylation of hormone-sensitive lipase (HSL) was repressed by the co-treatment with 15R. Moreover, the lipolysis was enhanced in the adipocyte-differentiated DP2R gene-knockout mouse embryonic fibroblasts. These results indicate that PGD2 suppressed the lipolysis by repression of the cAMP-PKA-HSL axis through DP2R in adipocytes.
=PGD2 ups lipid accumulation in adipocytes
Pronounced adipogenesis and increased insulin sensitivity caused by overproduction of prostaglandin D2 in vivo.
Fujitani Y1,
Aritake K,
Kanaoka Y,
Goto T,
Takahashi N,
Fujimori K,
Kawada T.
Author information
Abstract
Lipocalin-type prostaglandin (PG) D synthase is expressed in adipose tissues and involved in the regulation of glucose tolerance and atherosclerosis in type 2 diabetes. However, the physiological roles of PGD(2) in adipogenesis in vivo are not clear, as lipocalin-type prostaglandin D synthase can also act as a transporter for lipophilic molecules, such as retinoids. We generated transgenic (TG) mice overexpressing human hematopoietic PGDS (H-PGDS) and investigated the in vivo functions of PGD(2) in adipogenesis. PGD(2) production in white adipose tissue of H-PGDS TG mice was increased approximately seven-fold as compared with that in wild-type (WT) mice. With a high-fat diet, H-PGDS TG mice gained more body weight than WT mice. Serum leptin and insulin levels were increased in H-PGDS TG mice, and the triglyceride level was decreased by about 50% as compared with WT mice. Furthermore, in the white adipose tissue of H-PGDS TG mice, transcription levels of peroxisome proliferator-activated receptor gamma, fatty acid binding protein 4 and lipoprotein lipase were increased approximately two-fold to five-fold as compared with those of WT mice. Finally, H-PGDS TG mice showed clear hypoglycemia after insulin clamp.
These results indicate that TG mice overexpressing H-PGDS abundantly produced PGD(2) in adipose tissues, resulting in pronounced adipogenesis and increased insulin sensitivity. The present study provides the first evidence that PGD(2) participates in the differentiation of adipocytes and in insulin sensitivity in vivo, and the H-PGDS TG mice could constitute a novel model mouse for diabetes studies.
= PgD2 upregulation = hyper insulin-sensitivity and overexpressed adipogenesis(and sebocyte hyperprofileration. i have linked the studies about this b4 in this thread)
