Highlights in DD

Abstract

“Highlights” calls attention to exciting advances in developmental biology that have recently been reported in Developmental Dynamics. Development is a broad field encompassing many important areas. To reflect this fact, the section spotlights significant discoveries that occur across the entire spectrum of developmental events and problems: from new experimental approaches, to novel interpretations of results, to noteworthy findings utilizing different developmental organisms. Cells with potential (Functional Characterization of Cardiac Progenitor Cells and Their Derivatives in the Embryonic Heart Post-Chamber Formation by Nichole M. McMullen, Feixiong Zhang, Adam Hotchkiss, Frederic Bretzner, Jennifer M. Wilson, Hong Ma, Karim Wafa, Robert M. Brownstone, and Kishore B.S. Pasumarthi, Dev Dyn 238:2787–2799) In the E11.5 mouse heart, just after chamber formation, an astounding 40% of ventricular myocardial cells are undifferentiated. They express the cardiac induction transcription factor Nkx2.5, but lack differentiation markers like myofilaments and pro-atrial natriuretic factor (ANF) secretory granules. Here, McMullen et al. test whether the undifferentiated cells are cardiovascular cells-in-waiting. By assessing activity of three fluorescent reporters simultaneously, they saw that the majority of Nkx2.5+ cells could acquire expression of the cardiac differentiation markers myosin light chain (MLC2v) and ANF over time. Further experiments reveal that the resulting cell population is heterogeneous. Nkx2.5+MLC2v+ANF− cells are more likely to exhibit intracellular Ca2+ transients in response to pharmacological β-adrenergic receptor stimulation, suggesting they are functional cardiomyocytes. In contrast, evidence suggests that Nkx2.5+MLC2v+ANF+ cells have the potential to become conduction system cells. These cells are more likely to express conduction cell markers, connexin 40 and acetylcholinesterase. What's more, they only display Ca2+ transients when treated with pharmacological agents that block muscarinic receptors, Gi- and NOS-associated signaling pathways, which have been shown inhibit intracellular Ca2+ signaling in various cell types. Activation of these pathways may skew cells toward the conduction cell fate. Future in vivo experiments will determine whether the Nkx2.5+MLC2v−ANF− cardiac progenitor cells live up to their in vitro potentials. Stepwise progression (Progenitor Cell Maturation in the Developing Vertebrate Retina by Hyun-Jin Yang, Amila O. Silva, Naoko Koyano-Nakagawa, and Steven C. McLoon, Dev Dyn 238:2823–2836) Many teens wish they could do everything that adults can, but thankfully they must first acquire several characteristics. Yang and colleagues reasoned that, likewise, there are molecular characteristics that differentiate more mature neurogenic from preneurogenic retinal progenitor cells, only the former of which can produce daughter(s) that become postmitotic and differentiate. The authors combed the literature to find candidate gene expression that distinguishes between the progenitor cells. They find that the Notch ligand is expressed in proliferating cells of both types, the Notch ligand Delta1 is highly expressed in preneurogenic cells, and its expression is reciprocal with the basic helix-loop-helix transcription factor E2A, which labels proliferating neurogenic progenitors. To determine whether Notch signaling has a functional role, the pathway was inhibited in four ways including injection of antisense oligonucleotides to Delta1 and Notch. The results, expansion of neurogenic at the expense of preneurogenic progenitors, suggest that Notch maintains progenitors in a preneurogenic state. The authors also find that misexpression of Sonic hedgehog (Shh), which is expressed as cells transition to neurogenic progenitors, drives progenitors to the neurogenic state. They discuss possible reasons why their results with Notch and Shh differ from previously published results. Regardless, it is clear that like the transition to adulthood, maturation to neurogenic progenitors is carefully controlled. Zebrafish pin-ups (Normal Table of Postembryonic Zebrafish Development: Staging by Externally Visible Anatomy of the Living Fish by David M. Parichy, Michael R. Elizondo, Margaret G. Mills, Tiffany N. Gordon, and Raymond E. Engeszer, Dev Dyn 238:2975–3015) Countless zebrafish researchers have repeatedly ogled the embryonic staging tables that have adorned lab walls worldwide for the past 15 years. Scientists studying larvae, juveniles, and adults have meanwhile been denied the pleasures of standardized staging, compromising the ability to compare results between laboratories. At long last, this void has been filled. In their comprehensive study of easily visualized traits in postembryonic development, Parichy et al. first demonstrate that size (standard length, SL) is a more accurate indicator of developmental progress than counting days post fertilization. They thoughtfully take into consideration that it may be impractical to perform size measurements before experimentation, and include a conversion table to estimate live SL from post-fixation and post-in situ hybridization SLs. Next, comes a list of easily visible traits that denote developmental progress, including swim bladder changes, ossification progress, fin development, scale development and pigment patterns. Rich descriptions of each trait are accompanied by clearly-presented supporting statistical data. Finally, a series of postembryonic stages is designated by developmental milestones as related to size. Accompanying each stage are gorgeously photographed pictures of “reference individuals,” the long-awaited postembryonic zebrafish pin-ups.