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The arterial pole of the heart is the region where the ventricular myocardium continues as the vascular smooth muscle tunics of the aorta and pulmonary trunk. It has been shown that the arterial pole myocardium derives from the secondary heart field and the smooth muscle tunic of the aorta and pulmonary trunk derives from neural crest. However, this neural crest-derived smooth muscle does not extend to the arterial pole myocardium leaving a region at the base of the aorta and pulmonary trunk that is invested by vascular smooth muscle of unknown origin. Using tissue marking and vascular smooth muscle markers, we show that the secondary heart field, in addition to providing myocardium to the cardiac outflow tract, also generates prospective smooth muscle that forms the proximal walls of the aorta and pulmonary trunk. As a result, there are two seams in the arterial pole: first, the myocardial junction with secondary heart field-derived smooth muscle; second, the secondary heart field-derived smooth muscle with the neural crest-derived smooth muscle. Both of these seams are points where aortic dissection frequently occurs in Marfan's and other syndromes. Keywords: Heart development; Outflow tract; Arterial pole; Myocardium; Smooth muscle; Cardiac neural crest; Secondary heart field

In cardiac neural-crest-ablated embryos, the secondary heart field fails to add myocardial cells to the outflow tract and elongation of the tube is deficient (Yelbuz, T.M., Waldo, K.L., Kumiski, D.H., Stadt, H.A., Wolfe, R.R., Leatherbury, L., Kirby, M.L., 2002. Shortened outflow tract leads to altered cardiac looping after neural crest ablation. Circ. Res. 106, 504- 510). Since that study, we have shown that the secondary heart field provides both myocardium and smooth muscle to the arterial pole (Waldo, K.L., Hutson, M.R., Ward, C.C., Zdanowicz, M., Stadt, H.A., Kumiski, D., Abu-Issa, R., Kirby, M.L., 2005. Secondary heart field contributes myocardium and smooth muscle to the arterial pole of the developing heart. Dev. Biol. 281, 78-90). The present study was undertaken to determine whether addition of both cell types is disrupted after neural crest ablation. Marking experiments confirm that the myocardial component fails to be added to the outflow tract after neural crest ablation. The cells destined to go into the outflow myocardium fail to migrate and are left at the junction of the outflow myocardium with the nascent smooth muscle at the base of the arterial pole. In contrast, the vascular smooth muscle component is added to the arterial pole normally after neural crest ablation. When the myocardium is not added to the outflow tract, the point where the outflow joins the pharynx does not move caudally as it normally should, the aortic sac is smaller and fails to elongate resulting in abnormal connections of the outflow tract with the caudal aortic arch arteries. Keywords: Heart development; Outflow tract; Arterial pole; Myocardium; Smooth muscle; Cardiac neural crest ablation; Secondary heart field

Patterning of the ventral head has been attributed to various cell populations, including endoderm, mesoderm, and neural crest. Here, we provide evidence that head and heart development may be influenced by a ventral midline endodermal cell population. We show that the ventral midline endoderm of the foregut is generated directly from the extreme rostral portion of Hensen's node, the avian equivalent of the Spemann organizer. The endodermal cells extend caudally in the ventral midline from the prechordal plate during development of the foregut pocket. Thus, the prechordal plate appears as a mesendodermal pivot between the notochord and the ventral foregut midline. The elongating ventral midline endoderm delimits the right and left sides of the ventral foregut endoderm. Cells derived from the midline endoderm are incorporated into the endocardium and myocardium during closure of the foregut pocket and fusion of the bilateral heart primordia. Bilateral ablation of the endoderm flanking the midline at the level of the anterior intestinal portal leads to randomization of heart looping, suggesting that this endoderm is partitioned into right and left domains by the midline endoderm, thus performing a function similar to that of the notochord in maintaining left-right asymmetry. Because of its derivation from the dorsal organizer, its extent from the forebrain through the midline of the developing face and pharynx, and its participation in formation of a single midline heart tube, we propose that the ventral midline endoderm is ideally situated to function as a ventral organizer of the head and heart. Keywords: Axis; Development; Face; Head; Heart; Midline

Byline: Margaret L. Kirby (), with illustrations by Karen L. Waldo () Abstract: Development of the heart is a complex process involving primary and secondary heart fields that are set aside to generate myocardial and endocardial cell lineages. The molecular inductions that occur in the primary heart field appear to be recapitulated in induction and myocardial differentiation of the secondary heart field, which adds the conotruncal segments to the primary heart tube. While much is now known about the initial steps and factors involved in induction of myocardial differentiation, little is known about induction of endocardial development. Many of the genes expressed by nascent myocardial cells, which then become committed to a specific heart segment, have been identified and studied. In addition to the heart fields, several other 'extracardiac' cell populations contribute to the fully functional mature heart. Less is known about the genetic programs of extracardiac cells as they enter the heart and take part in cardiogenesis. The molecular/genetic basis of many congenital cardiac defects has been elucidated in recent years as a result of new insights into the molecular control of developmental events. Author Affiliation: () Department of Pediatrics, Division of Neonatology, Duke University Medical Center, Box 3179, Durham, NC 27710, USA, US Article History: Received Date: 18/10/2001 Accepted Date: 01/02/2002

A great deal is unclear about the process of cardiac outflow septation. Much controversy exists regarding the precise details of tissue origins and movements of various components. The contribution of the cardiac neural crest to aorticopulmonary and distal truncal septation has been described; however, the distribution of the neural crest in the proximal outflow and heart is unknown. The present study describes the movement of cardiac neural crest cells from the caudal pharyngeal arches into the outflow tract and base of the heart during the period of outflow septation. Using quail-chick chimeras we found that the cardiac neural crest was distributed to all levels of the outflow tract and into the base of the heart. Septation of the outflow tract lumen occurred by two different processes that involved the cardiac neural crest directly. Cardiac neural crest cells were also distributed to regions of the outflow tract that correlated with sites of remodeling, such as the aortic sac as it was remodeled into the base of the ascending aorta and pulmonary trunk, the distal truncus that was patterned into the two semilunar valves and in the proximal conotruncus where muscularization of the ridges and septum occurred. Additionally, cardiac neural crest cells were found at the site of closure of the ventricular septum, in the wall of the pulmonary infundibulum, and transiently in the wall of the aortic vestibule. Contrary to current thinking, not all of the condensed mesenchyme in the outflow tract during septation was derived from neural crest. Key Words: chick; quail-chick chimera; heart development; outflow septation; neural crest.

We used transgenic mice in which the promoter sequence for connexin 43 linked to a lacZ reporter was expressed in neural crest but not myocardial cells to document the pattern of cardiac neural crest cells in the caudal pharyngeal arches and cardiac outflow tract. Expression of lacZ was strikingly similar to that of cardiac neural crest cells in quail-chick chimeras. By using this transgenic mouse line to compare cardiac neural crest involvement in cardiac outflow septation and aortic arch artery development in mouse and chick, we were able to note differences and similarities in their cardiovascular development. Similar to neural crest cells in the chick, lacZ-positive cells formed a sheath around the persisting aortic arch arteries, comprised the aorticopulmonary septation complex, were located at the site of final fusion of the conal cushions, and populated the cardiac ganglia. In quail-chick chimeras generated for this study, neural crest cells entered the outflow tract by two pathways, submyocardially and subendocardially. In the mouse only the subendocardial population of lacZ-positive cells could be seen as the cells entered the outflow tract. In addition lacZ-positive cells completely surrounded the aortic sac prior to septation, while in the chick, neural crest cells were scattered around the aortic sac with the bulk of cells distributed in the bridging portion of the aorticopulmonary septation complex. In the chick, submyocardial populations of neural crest cells assembled on opposite sides of the aortic sac and entered the conotruncal ridges. Even though the aortic sac in the mouse was initially surrounded by lacZ-positive cells, the two outflow vessels that resulted from its septation showed differential lacZ expression. The ascending aorta was invested by lacZ-positive cells while the pulmonary trunk was devoid of lacZ staining. In the chick, both of these vessels were invested by neural crest cells, but the cells arrived secondarily by displacement from the aortic arch arteries during vessel elongation. This may indicate a difference in derivation of the pulmonary trunk in the mouse or a difference in distribution of cardiac neural crest cells. An independent mouse neural crest marker is needed to confirm whether the differences are indeed due to species differences in cardiovascular and/or neural crest development. Nevertheless, with the differences noted, we believe that this mouse model faithfully represents the location of cardiac neural crest cells. The similarities in location of lacZ-expressing cells in the mouse to that of cardiac neural crest cells in the chick suggest that this mouse is a good model for studying mammalian cardiac neural crest and that the mammalian cardiac neural crest performs functions similar to those shown for chick. Key Words: chick; mouse; connexin 43; quail-chick chimera; heart development; cardiac neural crest.

The complex multidisciplinary nature of neonatal intensive care combined with the numerous hand-offs occurring in this shift-based environment, requires efficient and clear communication and collaboration among staff to provide optimal care. However, the skills required to function as a team are not typically assessed, discussed, or even taught on a regular basis among neonatal personnel. We developed a multidisciplinary, small group, interactive workshop based on Team STEPPS to provide staff with formal teamwork skills, and to introduce new team-based practices; 129 (95%) of the eligible 136 staff were trained. We then compared the results of the pretraining survey (completed by 114 (84%) of staff) with the post-training survey (completed by 104 (81%) of participants) 2 years later. We found an improvement in the overall teamwork score from 7.37 to 8.08 (p=<0.0001) based on a range of poor (1) to excellent (9). Respondents provided higher ratings in 9 out of 15 team-based categories after the training. Specifically, staff found improvements in communication (p=0.037), placed greater importance on situation awareness (p=<0.00010), and reported that they supported each other more (p=<0.0001). Staff satisfaction was rated higher post-training, with responses showing that staff had greater job fulfilment (p=<0.0001), believed that their abilities were being utilised properly (p=0.003), and felt more respected (p=0.0037). 90% of staff found the new practice of team meetings to help increase awareness of unit acuity, and 77% of staff noted that they had asked for help or offered assistance because of information shared during these meetings. In addition to summarising the results of our training programme, this paper also provides practical tools that may be of use in developing team training programmes in other neonatal units.