Biomedical subjects

Zheng-Zheng Bao

Publications and source records attributed to Zheng-Zheng Bao.

6 recordsLinked to original sources

PubMed2006

Notch signaling plays a key role in cardiac cell differentiation.

Results from lineage tracing studies indicate that precursor cells in the ventricles give rise to both cardiac muscle and conduction cells. Cardiac conduction cells are specialized cells responsible for orchestrating the rhythmic contractions of the heart. Here, we show that Notch signaling plays an important role in the differentiation of cardiac muscle and conduction cell lineages in the ventricles. Notch1 expression coincides with a conduction marker, HNK-1, at early stages. Misexpression of constitutively active Notch1 (NIC) in early heart tubes in chick exhibited multiple effects on cardiac cell differentiation. Cells expressing NIC had a significant decrease in expression of cardiac muscle markers, but an increase in expression of conduction cell markers, HNK-1, and SNAP-25. However, the expression of the conduction marker connexin 40 was inhibited. Loss-of-function study, using a dominant-negative form of Suppressor-of-Hairless, further supports that Notch1 signaling is important for the differentiation of these cardiac cell types. Functional studies show that the expression of constitutively active Notch1 resulted in abnormalities in ventricular conduction pathway patterns.

Animals↗

PubMed2006

Sema3D, Sema3F, and Sema5A are expressed in overlapping and distinct patterns in chick embryonic heart.

An increasing number of axon guidance cues have been shown recently to play important roles in the development of non-neural tissues. Semaphorins comprise one of the largest conserved families of axon guidance factors. We analyzed the expression patterns of Sema3D, Sema3F, and Sema5A genes in the chick embryonic heart by in situ hybridization. All three genes are expressed in the cardiac cushion regions, both in the mesenchymal cells, and epithelial cells in the endocardial layer, during the period of cardiac remodeling. In addition to the overlapping expression patterns in the cardiac cushion regions, these genes also exhibit distinct expression patterns in the developing heart: Sema3D is additionally expressed in the tips of the ventricular trabeculae; Sema3F is expressed in a subset of cells scattered throughout the ventricles; and Sema5A is expressed in the newly formed atrioventricular valves. The overlapping and distinct expression patterns of these genes suggest that they may play important roles in heart development.

Animals↗

PubMed2006

Sema3D and Sema7A have distinct expression patterns in chick embryonic development.

By RT-PCR, we isolated a partial cDNA clone for the chick Semaphorin7A (Sema7A) gene. We further analyzed its expression patterns and compared them with those of the Sema3D gene, in chick embryonic development. Sema3D and Sema7A appeared to be expressed in distinct cell populations. In mesoderm-derived structures, Sema7A expression was detected in the newly formed somites, whereas Sema3D expression was found in the notochord. In ectoderm-derived tissues, Sema3D is expressed broadly in the surface ectoderm, lens and nasal placodes. Sema3D is also expressed in the developing nervous system including diencephalon, dorsal neural tube, optical and otic vesicles. In the limb bud, Sema3D expression was found throughout the ectoderm excluding the apical ectoderm ridge (AER), where Sema7A is concentrated. Although both genes appeared to be expressed in the migrating neural crest cells, Sema3D expression is limited to neural crest cells migrating out of the midbrain/hindbrain regions, while Sema7A expression is widespread in both cranial and trunk neural crest cells.

Amino Acid Sequence↗

PubMed2005

Sonic hedgehog has a dual effect on the growth of retinal ganglion axons depending on its concentration.

The stereotypical projection of retinal ganglion cell (RGC) axons to the optic disc has served as a good model system for studying axon guidance. By both in vitro and in vivo experiments, we show that a secreted molecule, Sonic hedgehog (Shh), may play a critical role in the process. It is expressed in a dynamic pattern in the ganglion cell layer with a relatively higher expression in the center of the retina. Through gel culture and stripe assays, we show that Shh has a dual effect on RGC axonal growth, acting as a positive factor at low concentrations and a negative factor at high concentrations. Results from time-lapse video microscopic and stripe assay experiments further suggest that the effects of Shh on axons are not likely attributable to indirect transcriptional regulation by Shh. Overexpression of Shh protein or inhibition of Shh function inside the retina resulted in a complete loss of centrally directed projection of RGC axons, suggesting that precise regulation of Shh level inside the retina is critical for the projection of RGC axons to the optic disc.

Age Factors↗

PubMed2004

Disruption of gradient expression of Zic3 resulted in abnormal intra-retinal axon projection.

The targeting of retinal ganglion axons toward the optic disc is the first step in axon pathfinding in the visual system. The molecular mechanisms involved in guiding the retinal axons to project towards the optic disc are not well understood. We report that a gene encoding a zinc-finger transcription factor, Zic3, is expressed in a periphery-high and center-low gradient in the retina at the stages of active axon extension inside the retina. The gradient expression of Zic3 recedes towards the periphery over the course of development, correlating with the progression of retinal cell differentiation and axonogenesis. Disruption of gradient expression of Zic3 by retroviral overexpression resulted in mis-targeting of retinal axons and some axons misrouted to the sub-retinal space at the photoreceptor side of the retina. Misexpression of Zic3 did not affect neurogenesis or differentiation inside the retina, or grossly alter retinal lamination. By stripe assay, we show that misexpression of Zic3 may induce the expression of an inhibitory factor to the retinal axons. Zic3 appears to play a role in intra-retinal axon targeting, possibly through regulation of the expression of specific downstream genes involved in axon guidance.

Animals↗

PubMed2003

Irx4-mediated regulation of Slit1 expression contributes to the definition of early axonal paths inside the retina.

Although multiple axon guidance cues have been discovered in recent years, little is known about the mechanism by which the spatiotemporal expression patterns of the axon guidance cues are regulated in vertebrates. We report that a homeobox gene Irx4 is expressed in a pattern similar to that of Slit1 in the chicken retina. Overexpression of Irx4 led to specific downregulation of Slit1 expression, whereas inhibition of Irx4 activity by a dominant negative mutant led to induction of Slit1 expression, indicating that Irx4 is a crucial regulator of Slit1 expression in the retina. In addition, by examining axonal behavior in the retinas with overexpression of Irx4 and using several in vivo assays to test the effect of Slit1, we found that Slit1 acts positively to guide the retinal axons inside the optic fiber layer (OFL). We further show that the regulation of Slit1 expression by Irx4 is important for providing intermediate targets for retinal axons during their growth within the retina.

Animals↗