Identification, characterization, and expression pattern of the chicken EKLF gene.

EKLF/KLF1 was the first of the Krüppel-like factors (KLFs) to be identified in mammals and plays an important role in primitive and definitive erythropoiesis. Here, we identify and characterize EKLF in the chicken (cEKLF). The predicted amino acid sequence of the zinc finger region of cEKLF is at least 87.7% similar to mammalian EKLF proteins and is 98.8% and 95% similar to the EKLF orthologues in Xenopus and zebrafish, respectively. During early embryonic development, cEKLF expression is seen in the posterior primitive streak, which gives rise to hematopoietic cells, and then in the blood islands and in circulating blood cells. cEKLF mRNA is expressed in blood cells but not in brain later in chicken embryonic development. cEKLF mRNA is increased in definitive compared with primitive erythropoiesis. The conserved sequence and expression pattern of cEKLF suggests that its function is similar to its orthologues in mammals, Xenopus, and zebrafish.     

Krüppel-like factors 4 and 5 expression and their involvement in differentiation of oral carcinomas

Proliferation-differentiation balance of epithelial cells is regulated by krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P < 0.05) and in parallel with the histological dedifferentiation (P = 0.09). Exogenous overexpression of KLF4 arranged cells in a cobble-like structure with desmosomes and KLF5 elongated cells like fibroblasts without desmosomes. KLF4 suppressed fibronectin expression, and KLF5 down-regulated and degraded E-cadherin. The proliferation was not affected by KLFs. Thus, down-regulation of KLF4 and up-regulation of KLF5 may stimulate oral carcinoma progression through the dedifferentiation of carcinoma cells.     

Krtippel样锌指因子在血液疾病中的研究进展

Krilppel,样锌指因子是真核生物中广泛存在的一类转录调控因子,参与细胞分化、增殖、凋亡和肿瘤形成等多种生理病理过程。其结构特点是羧基端高度保守,含有3个C2H2型锌指结构,与富含GC盒或CACCC序列的DNA结合;而氨基端的转录调控区在不同因子之间差异较大,发挥转录激活或转录抑制效应。现有研究显示多个Kriippel样锌指因子成员参与调控各类血细胞的生命活动。此文将就这几个与血液疾病发生有关的KLF样锌指因子作一概述。     

Skin-specific expression of ictacalcin, a homolog of the S100 genes, during zebrafish embryogenesis.

Full-length cDNA coding for the ictacalcin gene, a homolog of the S100 genes, was isolated in zebrafish and mapped on linkage group 16 using the LN54 radiation hybrid panel. The homology and phylogenetic analyses, based on the deduced amino acid sequences, showed the orthologous relationship of ictacalcin genes between zebrafish and other fish species. However, ictacalcin genes constitute an out-group with respect to other members of the S100 gene family. This result supports the findings that fish ictacalcin genes are new members of the S100 gene family and may have evolved after the divergence of teleosts and tetrapods. The zebrafish ictacalcin gene was zygotically transcribed from 12 hours postfertilization onward and was stably expressed throughout adulthood. During zebrafish embryogenesis, the ictacalcin gene was specifically expressed in striated epidermal cells covering the entire embryo. The ictacalcin staining in keratinocytes of striated epithelia was absent in the cytoplasm surrounding the nuclei, but it was highly concentrated in the peripheral margin. Tissues enriched with epithelia folds, such as olfactory epithelium, hatching gland, pectoral fin buds, urogenital opening, and pharynx, showed a robust ictacalcin expression. The strikingly heavy staining of ictacalcin in the pharyngeal region provides us with an early marker to follow the pharynx formation in zebrafish embryos.     

Altered expression of the KLF4 in colorectal cancers

KLF4 is an important regulator of cell proliferation and is maximally expressed in epithelial cells of the gastrointestinal tract. Inactivation of the KLF4 gene by genetic and epigenetic alterations has been reported in colorectal cancers, but the expression pattern of the KLF4 protein has not been studied. Here, to investigate the roles of KLF4 in colorectal carcinogenesis, we examined the expression pattern of the KLF4 protein in 123 colorectal cancers by immunohistochemistry using tissue microarray. Moderate to strong nuclear staining for KLF4 was found in normal colonic mucosa. Interestingly, loss of KLF4 expression was observed in 30 (24.4%) of 123 colorectal cancers. Statistically, loss of KLF4 protein expression was not associated with clinocopathologic parameters, including tumor stage (Bartholomew test, P>0.05), lymph node metastasis, differentiation, tumor location, and tumor size (chi2 test, P>0.05). These results indicate that loss of the KLF4 expression might play a role in tumor development as an early event for a subset of colorectal cancers.     

Expression patterns of Xenopus FGF receptor-like 1/nou-darake in early Xenopus development resemble those of planarian nou-darake and Xenopus FGF8.

Fibroblast growth factors (FGFs) mediate many cell-to-cell signaling events during early development. Nou-darake (ndk), a gene encoding an FGF receptor (FGFR)-like molecule, was found to be highly and specifically expressed in the head region of the planarian Dugesia japonica, and its functional analyses provided strong molecular evidence for the existence of a brain-inducing circuit based on the FGF signaling pathway. To analyze the role of ndk during vertebrate development, we isolated the Xenopus ortholog of ndk, the vertebrate FGFR-like 1 gene (XFGFRL1). Expression of XFGFRL1/Xndk was first detected in the anterior region at the late gastrula stage and dramatically increased at the early neurula stage in an overall anterior mesendodermal region, including the prechordal plate, paraxial mesoderm, anterior endoderm, and archenteron roof. This anterior expression pattern resembles that of ndk in planarians, suggesting that the expression of FGFRL1/ndk is conserved in evolution between these two distantly diverged organisms. During the tail bud stages, XFGFRL1/Xndk expression was detected in multiple regions, including the forebrain, eyes, midbrain-hindbrain boundary, otic vesicles, visceral arches, and somites. In many of these regions, XFGFRL1/Xndk was coexpressed with XFGF8, indicating that XFGFRL1/Xndk is a member of the XFGF8 synexpression group, which includes sprouty, sef, and isthmin.     

Reconstruction of cell lineage and spatiotemporal pattern formation of the mesoderm in the amphipod crustacean Orchestia cavimana

COVER PHOTOGRAPH: Collage of two developmental stages of the amphipod Orchestia cavimana. Both 3D‐reconstrucitons of CLSM image stacks. Lower image shows an early embryo (dorsal view) with labelled mesendodermal precursor cells of the trunk region in red (DiI in‐vivo labelling) and nuclei in blue (DAPI). Blastomeres ba and da were marked at 8‐cell stage. Upper image shows an advanced embryo shortly before hatching (lateral view) with musculature in red (Phalloidin) and nuclei in blue (DAPI). The segmental iterative musculature is a derivative of mesoblast cells which have the highly ordered pattern in earlier embryonic stages (shown below). From Hunnekuhl and Wolff, Developmental Dynamics 241:697–717, 2012.     

Analysis of origin and growth of the thyroid gland in zebrafish.

The zebrafish thyroid gland shows a unique pattern of growth as a differentiated endocrine gland. Here, we analyze the onset of differentiation, the contribution of lineages, and the mode of growth of this gland. The expression of genes involved in hormone production and the establishment of epithelial polarity show that differentiation into a first thyroid follicle takes place early during embryonic development. Thyroid follicular tissue then grows along the pharyngeal midline, initially independently of thyroid stimulating hormone. Lineage analysis reveals that thyroid follicle cells are exclusively recruited from the pharyngeal endoderm. The ultimobranchial bodies that merge with the thyroid in mammals form separate glands in zebrafish as visualized by calcitonin precursor gene expression. Mosaic analysis suggests that the first thyroid follicle differentiating at 55 hours postfertilization corresponds later to the most anterior follicle and that new follicles are added caudally.     

KLF4: a novel target for the treatment of atherosclerosis

Atherosclerosis is an inflammatory disease characterized by a large amount of hyperproliferation and poorly differentiated or undifferentiated smooth muscle cells in atherosclerotic plaque. Cancer cells differ from normal cells in many aspects, including hyperproliferation and loss of differentiation. So the research on tumor may shed light on the treatment of atherosclerosis. Given that Kruppel-like factor 4 (KLF4) has an important function in tumor development and progression, it may be associated with the formation and development of atherosclerosis. Recently, KLF4 expression has been documented in vascular endothelial cells. KLF4, which is normally not expressed in differentiated SMC in vivo, was rapidly up-regulated in response to vascular injury. In addition, KLF4 is a critical regulator in macrophage activation. Endothelial dysfunction, macrophage activation and VSMC phenotype switching are critical component elements in development of atherosclerosis. Herein we hypothesize that KLF4 is an important regulator in different phase of atherosclerosis and may be a novel target of prevention and cure of atherosclerosis. Further investigation is needed to approach the concrete signaling pathways about KLF4.