PubMed Health⌕ Search

Biomedical subjects

Chang-Soo Hong

Publications and source records attributed to Chang-Soo Hong.

5 recordsLinked to original sources

Functional analysis of Sox8 during neural crest development in Xenopus.

Among the families of transcription factors expressed at the neural plate border, Sox proteins have been shown to regulate multiple aspects of neural crest development. Sox8, Sox9 and Sox10, exhibit overlapping expression domains in neural crest progenitors, and studies in mouse suggest that Sox8 functions redundantly with Sox9 and Sox10 during neural crest development. Here, we show that in Xenopus, Sox8 accumulates at the lateral edges of the neural plate at the mid-gastrula stage; in contrast to its mouse and chick orthologs, Sox8 expression precedes that of Sox9 and Sox10 in neural crest progenitors. Later in development, Sox8 expression persists in migrating cranial crest cells as they populate the pharyngeal arches and in trunk neural crest cells, in a pattern that recapitulates both Sox9 and Sox10 expression domains. Although morpholino-mediated knockdown of Sox8 protein did not prevent the formation of neural crest progenitors, the timing of their induction was severely affected. This delay in neural crest specification had dramatic consequences on the development of multiple lineages of the neural crest. We demonstrate that these defects are due to the inability of neural crest cells to migrate into the periphery, rather than to a deficiency in neural crest progenitors specification and survival. These results indicate that the control of Sox8 expression at the neural plate border is a key process in initiating neural crest formation in Xenopus, and highlight species-specific differences in the relative importance of SoxE proteins during neural crest development.

Animals↗

The doublesex-related gene, XDmrt4, is required for neurogenesis in the olfactory system.

The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied. However, their expression pattern is not restricted to the gonad, suggesting that Dmrt genes might regulate other developmental processes. Here, we report the expression and functional analysis of one member of this family: Xenopus Dmrt4 (XDmrt4). XDmrt4 is initially expressed in the anterior neural ridge and then becomes progressively restricted to part of the telencephalon and the olfactory placode/epithelium. XDmrt4 is induced at the anterior neural plate by a balance of neural inducers and caudalizing factors. Interference with XDmrt4 function by injection of a morpholino oligonucleotide or an inhibitory mutant resulted in a similar phenotype, the specific disruption of the olfactory placode expression of Xebf2 without affecting the expression of other placodal markers. Xebf2 belongs to a family of helix-loop-helix transcription factors implicated in neuronal differentiation, and later in embryogenesis XDmrt4-deficient embryos show impaired neurogenesis in the olfactory epithelium. Consistent with this finding, XDmrt4 is sufficient to activate neurogenin, Xebf2, and neural cell adhesion molecule expression in animal explants and is required for Noggin-mediated neuralization. Altogether, these results indicate that XDmrt4 is an important regulator of neurogenesis in the olfactory system upstream of neurogenin and Xebf2.

Animals↗

Sox proteins and neural crest development.

Among the families of transcription factors expressed at the neural plate border in response to neural crest-inducing signals, Sox proteins have emerged as important players in regulating multiple aspects of neural crest development. Here, we summarize the expression of six Sox genes, namely Sox8, Sox9, Sox10, LSox5, Sox4 and Sox11, in neural crest progenitors and their derivatives, and review some aspects of their function pertaining to neural crest development in several species.

Animals↗

Early requirement of the transcriptional activator Sox9 for neural crest specification in Xenopus.

The neural crest is a multipotent population of cells that arises at the neural plate border in the vertebrate embryo. We have previously shown that a member of the Sox family of transcription factors, Sox9, is a regulator of neural crest formation in Xenopus, as Sox9-depleted embryos failed to form neural crest progenitors. Here, we describe experiments that further investigate Sox9 function during neural crest development. Induction of neural crest progenitors in Xenopus is regulated by Wnt signaling. We show that this process is largely dependent on Sox9 function as Wnt-mediated neural crest induction is inhibited in the context of Sox9-depleted embryos. Moreover, we demonstrate that Sox9 functions as a transcriptional activator during neural crest formation. Expression of a construct in which Sox9 DNA-binding domain (HMG box) is fused to the repressor domain of Drosophila engrailed blocked neural crest formation, thereby mimicking the phenotype of Sox9-depleted embryos. Finally, using a hormone-inducible inhibitory mutant of Sox9, lacking the transactivation domain, we show that Sox9 function is required for neural crest specification but not for its subsequent migration.

Animals↗

Cardiac remodeling and atrial fibrillation in transgenic mice overexpressing junctin.

Junctin is a 26-kDa integral membrane protein, colocalized with the ryanodine receptor (RyR) and calsequestrin at the junctional sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscles. To elucidate the functional role of junctin in heart, transgenic (TG) mice overexpressing canine junctin (24-29 folds) under the control of mouse a-myosin heavy chain promoter were generated. Overexpression of the junctin in mouse heart was associated with heart enlargements, bradycardia, atrial fibrillation, and increased fibrosis. Many ultrastructural alterations were observed in TG atria. The junctional SR cisternae facing transverse-tubules contained a dense matrix of calsequestrin in TG heart. According to echocardiography, TG mice showed enlarged left ventricles, dilated right atriums, and ventricles with paradoxical septal motion and impaired left ventricular systolic function. Overexpression of junctin led to down-regulation of triadin and RyR but to up-regulation of dihydropyridine receptor. The L-type Ca2+ current density and action potential durations increased, which could be the cause for the bradycardia in TG heart. This study provides an important example of pathogenesis leading to substantial cardiac remodeling and atrial fibrillation, which was caused by overexpression of junctin in heart.

Action Potentials↗