Highlights in DD


  • Julie C. Kiefer

“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.

A (r)evolutionary hypothesis (Neural Control of Gene Recruitment in Metazoans by Nelson R. Cabej, Dev Dyn240:1–8) From our school days onward, we are taught that metazoan evolution is driven by random mutations in DNA sequence that alter gene expression. In this fascinating, peer-reviewed “Perspectives” article, Cabej suggests that this widely held belief is just part of the story. He presents evidence of an inherent gene-recruiting mechanism, mediated by nervous system-driven epigenetic changes, that produce new or altered phenotypes independent of alterations in DNA sequence. The hypothesis hinges on the observation that metazoans are inextricably linked to their environment. Environmental stimuli, such as photoperiodicity, temperature, or visual cues, are received and processed by the nervous system. The nervous system then relays the message to pertinent organs by means of second messengers such as neuropeptides or hormones, a process that can alter gene expression in receiving cells. The author proposes that epigenetic changes within the pathway—such as changes in type or distribution of second messenger produced—can produce heritable phenotypes favored by natural selection. The startling implication is that metazoans have a malleable, built-in system that enables them to adapt to a changing environment, eliminating a dependence upon random, fortuitous initiating events. If experimental evidence catches up with the idea, get ready to re-write the textbooks.

Sculpting the heart (Hemodynamic Patterning of the Avian Atrioventricular Valve by Huseyin C. Yalcin, Akshay Shekhar, Tim C. McQuinn, and Jonathan T. Butcher, Dev Dyn240:23–35) Just as the Colorado River carved the Grand Canyon out of rock, blood flow sculpts the morphology of the developing heart. Although the phenomenon has been studied for 60 years, there has been little attempt to quantify influential hemodynamics. Here, Huseyin et al. combine micro-computed tomography (CT) with three-dimensional (3D) computational fluid dynamic (CFD) modeling to analyze hemodynamics of the chick atrioventricular (AV) canal during morphogenesis of the AV valves. When possible, direct in vivo measurements were used to validate model predictions and inform simulation parameters. CFD simulations reveal that hemodynamics either presage or correlate with morphological changes within the AV canal. For example at HH17, the wall shear stress experienced by the inner curvature of the tubular heart is nearly double that experienced by the outer curvature. At this time, the inner curvature initiates cardiac jelly expansion and endocardial to mesenchymal transformation required for cushion remodeling, while the outer curvature initiates jelly retraction and trabeculations. Such findings suggest that stress differences may be important for specifying the morphological changes. It has been suggested that a substantial fraction of congenital heart defects may derive from abnormal hemodynamics. Quantitative values measured by these methods may be useful for devising strategies to restore normal hemodynamics, and set the course straight.

Understanding MSC origins (Migration of Dorsal Aorta Mesenchymal Stem Cells Induced by Mouse Embryonic Circulation by Xin-Long Yan, Yu Lan, Xiao-Yan Wang, Wen-Yan He, Hui-Yu Yao, Dong-Bo Chen, Jia-Xiang Xiong, Jiao Gao, Zhuan Li, Guan Yang, Xiu-Sen Li, Yuan-Lin Liu, Ji-Yan Zhang, Bing Liu, and Ning Mao, Dev Dyn240:65–74) Mesenchymal stem cells (MSCs) have the remarkable ability to contribute toward homeostasis and repair of bone, cartilage, marrow stroma, muscle, fat, and tendon. Although MSCs have outstanding cell therapy potential, little is known about their in vivo characteristics. Here, Mao and colleagues rectify the shortcoming by investigating embryonic origins of MSCs. They find that, like hematopoietic stem cells (HSCs), canonical MSCs reside in the embryonic day (E) 11.5 embryonic dorsal aorta (DA), revealing the region as their possible site of origin. This localization, together with their finding that canonical MSCs express pericyte markers, agree with a previously proposed model that the perivascular zone operates as the MSC niche. The authors further show that MSCs are present in E12.5–E13.5 circulation, suggesting that they migrate to sites of action by means of the bloodstream, also similar to HSCs. In vitro assays demonstrate that the chemotaxis properties of embryonic blood are mediated by transforming growth factor-beta (TGF-β) and by platelet-derived growth factor-BB (PDGF-BB) signaling through the MAP Kinase pathway. The discovery of these migration and tissue integration properties are paramount to formulating strategies for MSC-based cell therapies.