Fates Aligned: Origins and Mechanisms of Ventricular Conduction System and Ventricular Wall Development.
The cardiac conduction system is a network of distinct cell types necessary for the coordinated contraction of the cardiac chambers. The distal portion, known as the ventricular conduction system, allows for the rapid transmission of impulses from the atrio-ventricular node to the ventricular myocardium and plays a central role in cardiac function as well as disease when perturbed. Notably, its patterning during embryogenesis is intimately linked to that of ventricular wall formation, including trabeculation and compaction. Here, we review our current understanding of the underlying mechanisms responsible for the development and maturation of these interdependent processes.
View details for PubMedID 29594502
Neonatal beta Cell Development in Mice and Humans Is Regulated by Calcineurin/NFAT
2012; 23 (1): 21-34
Little is known about the mechanisms governing neonatal growth and maturation of organs. Here we demonstrate that calcineurin/Nuclear Factor of Activated T cells (Cn/NFAT) signaling regulates neonatal pancreatic development in mouse and human islets. Inactivation of calcineurin b1 (Cnb1) in mouse islets impaired dense core granule biogenesis, decreased insulin secretion, and reduced cell proliferation and mass, culminating in lethal diabetes. Pancreatic ? cells lacking Cnb1 failed to express genes revealed to be direct NFAT targets required for replication, insulin storage, and secretion. In contrast, glucokinase activation stimulated Cn-dependent expression of these genes. Calcineurin inhibitors, such as tacrolimus, used for human immunosuppression, induce diabetes. Tacrolimus exposure reduced Cn/NFAT-dependent expression of factors essential for insulin dense core granule formation and secretion and neonatal ? cell proliferation, consistent with our genetic studies. Discovery of conserved pathways regulating ? cell maturation and proliferation suggests new strategies for controlling ? cell growth or replacement in human islet diseases.
View details for DOI 10.1016/j.devcel.2012.05.014
View details for Web of Science ID 000306583800007
View details for PubMedID 22814600
View details for PubMedCentralID PMC3587727
Deconstructing Pancreas Developmental Biology
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
2012; 4 (6)
The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development.
View details for DOI 10.1101/cshperspect.a012401
View details for Web of Science ID 000308028500015
View details for PubMedID 22587935
View details for PubMedCentralID PMC3367550
HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis
2008; 14 (2): 263-274
Repair of the programmed meiotic double-strand breaks (DSBs) that initiate recombination must be coordinated with homolog pairing to generate crossovers capable of directing chromosome segregation. Chromosome pairing and synapsis proceed independently of recombination in worms and flies, suggesting a paradoxical lack of coregulation. Here, we find that the meiotic axis component HTP-3 links DSB formation with homolog pairing and synapsis. HTP-3 forms complexes with the DSB repair components MRE-11/RAD-50 and the meiosis-specific axis component HIM-3. Loss of htp-3 or mre-11 recapitulates meiotic phenotypes consistent with a failure to generate DSBs, suggesting that HTP-3 associates with MRE-11/RAD-50 in a complex required for meiotic DSB formation. Loss of HTP-3 eliminates HIM-3 localization to axes and HIM-3-dependent homolog alignment, synapsis, and crossing over. Our study reveals a mechanism for coupling meiotic DSB formation with homolog pairing through the essential participation of an axis component with complexes mediating both processes.
View details for DOI 10.1016/j.devce1.2007.11.016
View details for Web of Science ID 000253241400015
View details for PubMedID 18267094
Social learning and innovation are positively correlated in pigeons (Columba livia)
2007; 10 (2): 259-266
When animals show both frequent innovation and fast social learning, new behaviours can spread more rapidly through populations and potentially increase rates of natural selection and speciation, as proposed by A.C. Wilson in his behavioural drive hypothesis. Comparative work on primates suggests that more innovative species also show more social learning. In this study, we look at intra-specific variation in innovation and social learning in captive wild-caught pigeons. Performances on an innovative problem-solving task and a social learning task are positively correlated in 42 individuals. The correlation remains significant when the effects of neophobia on the two abilities are removed. Neither sex nor dominance rank are associated with performance on the two tasks. Free-flying flocks of urban pigeons are able to solve the innovative food-finding problem used on captive birds, demonstrating it is within the range of their natural capacities. Taken together with the comparative literature, the positive correlation between innovation and social learning suggests that the two abilities are not traded-off.
View details for DOI 10.1007/s10071-006-0064-1
View details for Web of Science ID 000246138500018
View details for PubMedID 17205290
Finding and keeping your partner during meiosis
2004; 3 (8): 1014-1016
HIM-3 is a meiosis-specific protein that localizes to the cores of chromosomes from the earliest stages of prophase I until the metaphase to anaphase I transition in Caenorhabditis elegans. him-3 mutations disrupt homolog alignment, synapsis, and recombination and we propose that the association of HIM-3 with chromosome axes is a critical event in meiotic chromosome morphogenesis that is required for the proper coordination of these processes. The presence of HIM-3-like proteins in other eukaryotes, some of which are known to be required for synapsis and recombination, suggests the existence of a conserved class of axis-associated proteins that function at the junction of essential meiotic processes.
View details for Web of Science ID 000224088700014
View details for PubMedID 15280669