Developmental Dynamics

doi: 10.1002/dvdy.22436pmid: N/A

Kiefer, Julie C.

doi: 10.1002/dvdy.22390pmid: N/A

Ni, Amy; Lashnits, Erin; Yao, Li‐Chin; Baluk, Peter; McDonald, Donald M.

doi: 10.1002/dvdy.22435pmid: N/A

Hypoxia and vascular remodeling in postnatal mouse trachea. Confocal image of whole mount of P3 mouse trachea stained for hypoxic cells (pimonidazole, green) and blood vessels (PECAM‐1, red). Blood vessels survive in hypoxic regions (green), but are absent or dying in vertically‐oriented dark regions that are not hypoxic, which are located mostly over regions containing cartilage. From Ni et al., Developmental Dynamics 239:2354–2366, 2010.

Carey, John C.

doi: 10.1002/dvdy.22385pmid: N/A

Wang, Ying‐Hsuan; Huang, Min‐Lang

doi: 10.1002/dvdy.22394pmid: 20737505

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is one of the main signaling pathways in eukaryotic cells. This pathway is used during diverse growth and developmental processes in multiple tissues to control cell proliferation, differentiation, survival, and apoptosis. In addition to its role during development, the JAK/STAT pathway has also been implicated in tumorigenesis. Drosophila melanogaster is a powerful genetic tool, and its eyes have been used extensively as a platform to study signaling pathways. Many reports have demonstrated that the JAK/STAT pathway plays pleiotropic roles in Drosophila eye development. Its functions and activation are decided by its interplay with other signal pathways and the epigenetic status. In this review, we focus on the functions and regulation of the JAK/STAT pathway during eye development and provide some insights into the study of this pathway in tumorigenesis. Developmental Dynamics 239:2522–2533, 2010. © 2010 Wiley‐Liss, Inc.

Wise, Sarah B.; Stock, David W.

doi: 10.1002/dvdy.22411pmid: 21038444

Bone morphogenetic protein (Bmp) signaling has been shown to play important roles in tooth development at virtually all stages from initiation to hard tissue formation. The specific ligands involved in these processes have not been directly tested by loss‐of‐function experiments, however. We used morpholino antisense oligonucleotides and mutant analysis in the zebrafish to reduce or eliminate the function of bmp2b and bmp4, two ligands known to be expressed in zebrafish teeth and whose mammalian orthologs are thought to play important roles in tooth development. Surprisingly, we found that elimination of function of these two genes singly and in combination did not prevent the formation of mature, attached teeth. The mostly likely explanation for this result is functional redundancy with other Bmp ligands, which may differ between the zebrafish and the mouse. Developmental Dynamics 239:2534–2546, 2010. © 2010 Wiley‐Liss, Inc.

Winslow, B.B.; Burke, A.C.

doi: 10.1002/dvdy.22388pmid: 20730871

Development of synovial joints involves generation of cartilaginous anlagen, formation of interzones between cartilage anlagen, and cavitation of interzones to produce fluid filled cavities. Interzone development is not fully understood, but interzones are thought to develop from skeletogenic cells that are inhibited from further chondrogenic development by a cascade of gene expression including Wnt and Bmp family members. We examined the development of the rarely studied avian costal joint to better understand mechanisms of joint development. The costal joint is found within ribs, is morphologically similar to the metatarsophalangeal joint, and undergoes cavitation in a similar manner. In contrast to other interzones, Wnt14/9a, Gdf5, Chordin, Barx1, and Bapx1 are absent from the costal joint interzone, consistent with the absence of active β‐catenin and phosphorylated Smad 1/5/8. However Autotaxin and Noggin are expressed. The molecular profile of the costal joint suggests there are alternative mechanisms of interzone development. Developmental Dynamics 239:2547–2557, 2010. © 2010 Wiley‐Liss, Inc.

Yoshida, Toshiyuki; Miyoshi, Jun; Takai, Yoshimi; Thesleff, Irma

doi: 10.1002/dvdy.22395pmid: 21038445

Nectins are immunoglobulin‐like cell adhesion proteins and their interactions recruit various cell–cell junctions. Mutations in human NECTIN‐1 cause an ectodermal dysplasia syndrome, but Nectin‐1 null mice have only slight defects in teeth, suggesting compensation by other nectin(s). We observed overlapping expression of nectin‐3 with nectin‐1 and enamel abnormality in the nectin‐3 mutant. We, therefore, generated nectin‐1;nectin‐3 compound mutants. However, all teeth developed and no significant dental abnormalities were observed before birth. At postnatal day 10, the upper molars of compound mutants exhibited conical crown shape and retarded enamel maturation. Nectin‐1 was expressed in ameloblasts whereas nectin‐3 was expressed in neighboring stratum intermedium cells at this stage. The immunohistochemical localization and electron microscopical observations indicated that the desmosomal junctions between stratum intermedium and ameloblasts were significantly reduced. These results suggest that heterophilic interaction between nectin‐1 and nectin‐3 recruits desmosomal junctions, and that these are required for proper enamel formation. Developmental Dynamics 239:2558–2569, 2010. © 2010 Wiley‐Liss, Inc.

Enciso, Josephine M.; Konecny, Christine M.; Karpen, Heidi E.; Hirschi, Karen K.

doi: 10.1002/dvdy.22389pmid: 20737513

The molecular mechanism(s) controlling cell migration during vascular morphogenesis in vivo remain largely undefined. To address this within a physiological context, we used retinaldehyde dehydrogenase‐2 (Raldh2) null mouse embryos and demonstrate that retinoic acid (RA) deficiency results in abnormal yolk sac vascular remodeling due to decreased Rac1 activation, increased RhoA activation, and increased focal adhesions. Vinculin was increased in Raldh2−/− yolk sacs, and molecular events important for focal adhesion turnover, FAK phosphorylation (Tyr397) and FAK‐paxillin association, were decreased. RA‐rescue of vascular remodeling down‐regulated vinculin and restored FAK phosphorylation (Tyr397) and FAK‐paxillin association. Furthermore, vascular rescue with vascular endothelial growth factor‐A, Indian hedgehog, and basic fibroblast growth factor restored FAK phosphorylation (Tyr397) in the endothelium of Raldh2−/− yolk sacs. Our results provide new insights into the regulation of endothelial cell migration during vascular remodeling in vivo by adding the Rac1 and FAK activation pathway as a critical mediator of focal adhesion formation and turnover during vascular remodeling. Developmental Dynamics 239:2570–2583, 2010. © 2010 Wiley‐Liss, Inc.

Stanic, Karen; Montecinos, Hernán; Caprile, Teresa

doi: 10.1002/dvdy.22387pmid: 20730872

The subcommissural organ (SCO) is a roof plate differentiation located in the caudal diencephalon under the posterior commissure (PC). A role for SCO and its secretory product, SCO‐spondin, in the formation of the PC has been proposed. Here, we provide immunohistochemical evidence to suggest that SCO is anatomically divided in a bilateral region positive for SCO‐spondin that surrounds a negative medial region. Remarkably, axons contacting the lateral region are highly fasciculated, in sharp contrast with the defasciculated axons of the medial region. In addition, lateral axon fascicles run toward the midline inside of tunnels limited by the basal prolongations of SCO cells and extracellular SCO‐spondin. Our in vitro data in collagen gel matrices show that SCO‐spondin induces axonal growth and fasciculation of pretectal explants. Together, our findings support the idea that SCO‐spondin participates in the guidance and fasciculation of axons of the PC. Developmental Dynamics 239:2584–2593, 2010. © 2010 Wiley‐Liss, Inc.