Recent Papers

From Embryology

Recent papers in embryology appearing in the journals.

Stem Cells

This Genes & Development paper shows that differentiation regulation at the RNA level can be found, and may well be significant within stem cells. This regulation was identified by the presence of a number of small RNA regulatory factors.

Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs Joshua E. Babiarz, J. Graham Ruby, Yangming Wang, David P. Bartel, and Robert Blelloch Genes Dev. 2008;22 2773-2785

“Our results extend the known diversity of mammalian small RNA-generating pathways and show that mammalian siRNAs exist in cell types other than oocytes.”

Liver Development

This paper in Drug Metabolism Dispos describes how the newborn liver continues to differentiate postnatally. Remember that just because the organ looks like the mature form, does not mean that it yet functions like the adult organ. This may also relate to the changes that occur in human postnatal drug clearance rates. (More? UNSW Embryology - Liver Development)

Hart SN, Cui Y, Klaassen CD, Zhong XB. THREE PATTERNS OF CYTOCHROME P450 GENE EXPRESSION DURING LIVER MATURATION IN MICE. Drug Metab Dispos. 2008 Oct 9. [Epub ahead of print] PMID: 18845660

“To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (Cyps) in mice

… the developmental expression of Cyps in (neonatal) mouse liver can be divided into three patterns, suggesting different mechanisms responsible for the expression of Cyps during liver maturation.”

Cardiovascular Development

This Development paper shows yet another role for the Wnt signaling pathway in early vascular development, differentiation of angioblasts, and through R-spondin 3 (Rspo3) is linked into the vascular endothelial growth factor (VEGF) signaling pathway. (More? UNSW Embryology Cardiovascular and Blood Vessel Development)

Kazanskaya O, Ohkawara B, Heroult M, Wu W, Maltry N, Augustin HG, Niehrs C. The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development. Development. 2008 Oct 8. [Epub ahead of print] PMID: 18842812

“R-spondin 3 (Rspo3), a member of a novel family of secreted proteins in vertebrates that activate Wnt/beta-catenin signaling, plays a key role in these processes.”

Neural - Peripheral Nervous System

Directional growth in neuronal processes appears to be regulated by a series of repulsive and attractive environmental factors.

This J. Neuroscience paper looks at the signals involved and required for guiding the neural crest derived dorsal root ganglion (DRG) neuron axons into the spinal cord. Netrin-1 is a secreted protein (70-80 kD) growth factor made by floor plate cells. In other developing neuronal systems (spinal commissural axons) the same factor acts as an axonal chemoattractant. Netrin-1 in mammals has three receptors UNC5H1, UNC5H2, and UNC5H3 (human also named UNC5A, UNC5B, and UNC5C). (More? UNSW Embryology - Neural Crest and Neural Development | OMIM - Netrin-1)

Netrin-1 Acts as a Repulsive Guidance Cue for Sensory Axonal Projections toward the Spinal Cord Tomoyuki Masuda, Keisuke Watanabe, Chie Sakuma, Kazuhiro Ikenaka, Katsuhiko Ono, and Hiroyuki Yaginuma J. Neurosci. 2008;28 10380-10385

Muscle Development

The key transcription factors in muscle determination and early development were identified some years ago and served as a “paradigm” model for cell type differention during development. This recent article in Molecular Cell closely studies the molecular mechanisms and factors involved in a key step in this signaling process. (UNSW Embryology - Muscle Development | Molecular Development Signaling)

MyoD Targets TAF3/TRF3 to Activate Myogenin Transcription M.D.E. Deato, M.T. Marr, T. Sottero, C. Inouye, P. Hu, and R. Tjian Molecular Cell, Vol 32, 96-105, 10 October 2008

“Here, we report the development of a purified reconstituted system to analyze the properties of a TAF3/TRF3 complex in directing transcription initiation at the Myogenin promoter. Importantly, this new complex is required to replace the canonical TFIID to recapitulate MyoD-dependent activation of Myogenin. In vitro and cell-based assays identify a domain of TAF3 that mediates coactivator functions targeted by MyoD. Our findings also suggest changes to CRSP/Mediator in terminally differentiated myotubes. This switching of the core promoter recognition complex during myogenesis allows a more balanced division of labor between activators and TAF coactivators, thus providing another strategy to accommodate cell-specific regulation during metazoan development.”

Heart Development

Embryonic stem (ES) cells transfected to induced to express Notch 4 receptor respecify hemangioblast cell to a cardiac fate (cardiomyocytes). This paper while looking at developing cardiomyocytes for cardiac replacement also looks at the underlying signaling pathways required for their original embryonic differentiation.

Nature Biotechnology

Vincent C Chen, Robert Stull, Daniel Joo, Xin Cheng and Gordon Keller Notch signaling respecifies the hemangioblast to a cardiac fate pp1169 - 1178 Nature Biotechnology 26, 1169 - 1178 (2008) Published online: 28 September 2008 | doi:10.1038/nbt.1497

This JCB paper identifies a signaling pathway involving: Notch -> cyclin D1 nuclear localization -> regulation of cell cycle reentry.

They also suggest that “Notch triggers the DNA damage checkpoint and G2/M interphase arrest. ” which leads to the loss of proliferative ability with age.

The Journal of Cell Biology, Vol. 183, No. 1, 129-141

Notch activates cell cycle reentry and progression in quiescent cardiomyocytes Victor M. Campa, Raquel Gutierrez-Lanza, Fabio Cerignoli, Ramon Diaz-Trelles, Brandon Nelson, Toshiya Tsuji, Maria Barcova, Wei Jiang, and Mark Mercola J. Cell Biol. 2008;183 129-141, Published online Oct 6 2008, 10.1083/jcb.200806104.