Disease relevance of cdx4

• The differentiation of these GABAergic markers occurs first in the first brain nerves and the cerebral ganglion and then with a several-hour delay in the caudal ganglion [1].
• In addition, hemorrhage was observed at the caudal side of the eye [2].
• These results demonstrate that zebrafish caudal fin regeneration is a unique model to investigate molecular mechanism(s) of TCDD toxicity [3].

High impact information on cdx4

• Some ventralized mutants recover and develop into fertile adults, thereby revealing a requirement for chd function for the later processes of fin and caudal skeletal patterning [4].
• The profiles were obtained from larger-scale sequencing of small RNA libraries prepared from developmentally staged zebrafish, and two adult fibroblast cell lines derived from the caudal fin (ZFL) and the liver epithelium (SJD) [5].
• Truncate (tc) is an autosomal recessive mutation in mouse that specifically disrupts the development of the caudal notochord [6].
• PTH2 receptor expression is greatest in the CNS, where it is concentrated in limbic, hypothalamic, and sensory areas, especially hypothalamic periventricular neurons, nerve terminals in the median eminence, superficial layers of the spinal cord dorsal horn, and the caudal part of the sensory trigeminal nucleus [7].
• Secreted from the anterior boundary of the zebrafish neural plate, Tlc appears to protect the telencephalon from obliteration by a more caudal neural Wnt signal [8].

Biological context of cdx4

• Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression [9].
• Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis [9].
• Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression [9].
• The AN enhancer has activity in the entire anterior neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm [10].
• This phenotype cannot be explained by caudal vessel abnormalities or by a defect in cranial vessel patterning, but instead stems from an increase in endothelial cell number in specific cranial vessels [11].

Anatomical context of cdx4

• Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development [9].
• Inhibiting the caudal-related genes cdx1a and cdx4 in zebrafish embryos caused ectopic expression of genes that are normally expressed in the posterior hindbrain and anterior spinal cord, and ectopic formation of the hindbrain motor and commissure neurons in the posteriormost neural tissue [12].
• In zebrafish, mutations in cdx4 cause a severe, but not complete, deficit in embryonic blood cells [13].
• The zebrafish gene valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and valentino mutants lack visible hindbrain segmentation caudal to the r3/4 boundary (Moens, C. B., Yan, Y.-L., Appel, B., Force, A. G., and Kimmel, C. B. (1996) Development 122, 3981-3990) [14].
• By 24 hours L3 is expressed throughout the midbrain including the region of the presumptive tectum whereas L4 is strongly expressed in the midbrain caudal to the presumptive tectum [15].

Associations of cdx4 with chemical compounds

• A zebrafish retinoic acid receptor expressed in the regenerating caudal fin [16].
• Unlike zebrafish intraflagellar transport protein (IFT) mutants, cyst formation was not associated with cilia defects and instead correlated with reduced kidney fluid output, expansion of caudal duct apical cell membranes, and occlusion of the caudal pronephric nephron segment [17].
• Our finding that HS6ST-2 is required for the branching morphogenesis of the caudal vein is the first in vivo evidence for an essential role of a gene encoding a heparan sulfate modifying enzyme in vertebrate angiogenesis [18].
• The histamine-storing neurons were only seen in the caudal hypothalamus, around the posterior recess of the diencephalic ventricle [19].
• Antibodies to neuropeptide Y, dopamine-beta-hydroxylase, and serotonin labeled fibers in the olfactory bulb and cell bodies in caudal regions of the brain in distributions comparable to other species [20].

Regulatory relationships of cdx4

• Here, we report the dynamic and restricted expression of three zebrafish barhl within the developing central nervous system. barhl2 becomes expressed in the late gastrula as a transverse diencephalic domain located immediately caudal to the prospective eyes [21].
• Ectopic expression of mdk2 enhances neural crest cell fates at the lateral edges of the caudal neural plate, concomitant with a repression of anterior structures and mesendodermal and ectodermal markers [22].
• Zebrafish keratin 8 is expressed at high levels in the epidermis of regenerating caudal fin [23].
• Plasticin is expressed also in reticulospinal neurons and in caudal primary motoneurons [24].

Other interactions of cdx4

• Furthermore, this method provided direct evidence for a functional role for msxb in caudal fin regeneration [25].
• Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine [26].
• These studies demonstrate that, in zebrafish, spi1 marks a rostral population of LPM cells committed to a myeloid fate anatomically separated from and developmentally independent of erythroid commitment in the caudal LPM [27].
• Both wt1a and wt1b are expressed in the intermediate mesoderm, with wt1b being restricted to a smaller area lying at the caudal end of the wt1a expression domain [28].
• We show here that vhnf1 functions in two ways to subdivide the zebrafish caudal hindbrain domain (r4-r7) into individual rhombomeres [29].

Analytical, diagnostic and therapeutic context of cdx4

• Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes [26].
• Confocal laser microscopy of embryos 40 and 48 hpf also showed a nonmobile population of GFP+ cells in a discrete area between the dorsal aorta and caudal vein [30].
• Immunohistochemistry for gamma-aminobutyric acid (GABA) revealed that GABA is produced at all sites of GAD expression, including the novel cells in the caudal hindbrain [31].
• In situ hybridization revealed expression in the mesenchyme between cartilage condensations of the endoskeletal supports of the dorsal, anal, and caudal fins [32].
• In this study, electrophysiological recordings from cichlid Mauthner neurons showed that visual stimulation of the caudal retina (by a rostral cue) generates a depolarization that is about 1.5 times the amplitude of that generated by stimulation of the rostral retina (by a caudal cue) [33].

References