Person:
Zhao, Long

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Zhao

First Name

Long

Name

Zhao, Long
Author's Publications: search.filters.isAuthorOfPublication.f1ed30eb-b532-4965-9571-55cefa02cf06

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    The emerging roles of phosphatases in Hedgehog pathway
    (BioMed Central, 2017) Zhao, Long; Wang, Liguo; Chi, Chunli; Lan, Wenwen; Su, Ying
    Hedgehog signaling is evolutionarily conserved and plays a pivotal role in cell fate determination, embryonic development, and tissue renewal. As aberrant Hedgehog signaling is tightly associated with a broad range of human diseases, its activities must be precisely controlled. It has been known that several core components of Hedgehog pathway undergo reversible phosphorylations mediated by protein kinases and phosphatases, which acts as an effective regulatory mechanism to modulate Hedgehog signal activities. In contrast to kinases that have been extensively studied in these phosphorylation events, phosphatases were thought to function in an unspecific manner, thus obtained much less emphasis in the past. However, in recent years, increasing evidence has implicated that phosphatases play crucial and specific roles in the context of developmental signaling, including Hedgehog signaling. In this review, we present a summary of current progress on phosphatase studies in Hedgehog pathway, emphasizing the multiple employments of protein serine/threonine phosphatases during the transduction of morphogenic Hedgehog signal in both Drosophila and vertebrate systems, all of which provide insights into the importance of phosphatases in the specific regulation of Hedgehog signaling.
  • Thumbnail Image
    Publication
    Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration
    (Proceedings of the National Academy of Sciences, 2014) Zhao, Long; Borikova, Asya; Ben-Yair, Raz; Guner-Ataman, Burcu; MacRae, Calum; Lee, Richard; Burns, Charles; Burns, Caroline
    The human heart’s failure to replace ischemia-damaged myocardium with regenerated muscle contributes significantly to the worldwide morbidity and mortality associated with coronary artery disease. Remarkably, certain vertebrate species, including the zebrafish, achieve complete regeneration of amputated or injured myocardium through the proliferation of spared cardiomyocytes. Nonetheless, the genetic and cellular determinants of natural cardiac regeneration remain incompletely characterized. Here, we report that cardiac regeneration in zebrafish relies on Notch signaling. Following amputation of the zebrafish ventricular apex, Notch receptor expression becomes activated specifically in the endocardium and epicardium, but not the myocardium. Using a dominant negative approach, we discovered that suppression of Notch signaling profoundly impairs cardiac regeneration and induces scar formation at the amputation site. We ruled out defects in endocardial activation, epicardial activation, and dedifferentiation of compact myocardial cells as causative for the regenerative failure. Furthermore, coronary endothelial tubes, which we lineage traced from preexisting endothelium in wild-type hearts, formed in the wound despite the myocardial regenerative failure. Quantification of myocardial proliferation in Notch-suppressed hearts revealed a significant decrease in cycling cardiomyocytes, an observation consistent with a noncell autonomous requirement for Notch signaling in cardiomyocyte proliferation. Unexpectedly, hyperactivation of Notch signaling also suppressed cardiomyocyte proliferation and heart regeneration. Taken together, our data uncover the exquisite sensitivity of regenerative cardiomyocyte proliferation to perturbations in Notch signaling.
  • Thumbnail Image
    Publication
    Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis
    (2016) Han, Peidong; Bloomekatz, Joshua; Ren, Jie; Zhang, Ruilin; Grinstein, Jonathan D.; Zhao, Long; Burns, C. Geoffrey; Burns, Caroline; Anderson, Ryan M.; Chi, Neil C.
    Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart is comprised of an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease (CHD)1 and non-compaction cardiomyopathies2, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here, we utilize advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signaling that directs the spatial allocation of myocardial cells to their proper morphologic positions in the ventricular wall. Although previous studies have shown that endocardial Notch signaling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and BMP signaling3, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signaling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness due to excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell thick wall but no trabeculae. Notably, this myocardial Notch signaling is activated non-cell-autonomously by neighboring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provides insight into the cellular dynamics of how diverse cell lineages organize to create form.