Conditional fluorescent mouse translocation reporters for ERK1/2 and AKT signaling.

Understanding how cells activate intracellular signaling pathways in response to external signals, such as growth factors, is a longstanding goal of cell and developmental biology. Recently, live-cell signaling reporters have greatly expanded our understanding of signaling dynamics in response to wide-ranging stimuli and chemical or genetic perturbation, both ex vivo (cell lines) and in vivo (whole embryos or animals). Among the many varieties of reporter systems, translocation reporters that change sub-cellular localization in response to pathway activation have received considerable attention for their ease of use compared to FRET systems and favorable response times compared to transcriptional reporters.

The Wnt1-Cre2 transgene is active in the male germline.

The Wnt1-Cre transgenic mouse line is widely used to express the CRE recombinase in neural crest lineages, but it overexpresses WNT1 itself, which can cause undesired phenotypes. To address this, we and others previously developed a Wnt1-Cre2 line based on the same regulatory elements as Wnt1-Cre but without ectopic Wnt1 expression. However, while Wnt1-Cre2 exhibits normal activity when transmitted from female mice, it exhibits unexpected activity in the male germline.

Differential regulation of cranial and cardiac neural crest by serum response factor and its cofactors.

Serum response factor (SRF) is an essential transcription factor that influences many cellular processes including cell proliferation, migration, and differentiation. SRF directly regulates and is required for immediate early gene (IEG) and actin cytoskeleton-related gene expression. SRF coordinates these competing transcription programs through discrete sets of cofactors, the ternary complex factors (TCFs) and myocardin-related transcription factors (MRTFs).

FGF signaling regulates development by processes beyond canonical pathways.

FGFs are key developmental regulators that engage a signal transduction cascade through receptor tyrosine kinases, prominently engaging ERK1/2 but also other pathways. However, it remains unknown whether all FGF activities depend on this canonical signal transduction cascade. To address this question, we generated allelic series of knock-in and mouse strains, carrying point mutations that disrupt binding of signaling effectors, and a kinase dead allele of that broadly phenocopies the null mutant.

A most formidable arsenal: genetic technologies for building a better mouse.

The mouse is one of the most widely used model organisms for genetic study. The tools available to alter the mouse genome have developed over the preceding decades from forward screens to gene targeting in stem cells to the recent influx of CRISPR approaches. In this review, we first consider the history of mice in genetic study, the development of classic approaches to genome modification, and how such approaches have been used and improved in recent years.

A Fateful Decision: Tgif1 and Cardiac Neural Crest Identity.

Neural crest cells have different developmental potencies at different levels along the body axis of the embryo. In this issue of Developmental Cell, Gandhi et al. identify transcription factors that define one subtype of neural crest, the cardiac crest, and demonstrate their ability to reprogram trunk into cardiac crest.

MAPK and PI3K signaling: At the crossroads of neural crest development.

Receptor tyrosine kinase-mediated growth factor signaling is essential for proper formation and development of the neural crest. The many ligands and receptors implicated in these processes signal through relatively few downstream pathways, frequently converging on the MAPK and PI3K pathways. Despite decades of study, there is still considerable uncertainty about where and when these signaling pathways are required and how they elicit particular responses.

Endothelial primary cilia inhibit atherosclerosis.

Primary cilia are microtubule-based structures present on most mammalian cells that are important for intercellular signaling. Cilia are present on a subset of endothelial cells where they project into the vessel lumen and are implicated as mechanical sensors of blood flow. To test the in vivo role of endothelial cilia, we conditionally deleted Ift88, a gene required for ciliogenesis, in endothelial cells of mice.

Hedgehog signaling controls T cell killing at the immunological synapse.

The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling.

Fibrillin-2b regulates endocardial morphogenesis in zebrafish.

scotch tape (sco) is a zebrafish cardiac mutant initially proposed to exhibit a reduced amount of cardiac jelly, the extracellular matrix between the myocardial and endocardial layers. We analyzed sco(te382) mutant hearts in detail using both selective plane illumination microscopy (SPIM) and transmission electron microscopy (TEM), and observed a fascinating endocardial defect. Time-lapse SPIM imaging of wild-type and mutant embryos revealed significant and dynamic gaps between endocardial cells during development.

Function of ammonium transporter A in the initiation of culmination of development in Dictyostelium discoideum.

The histidine kinase DhkC controls a phosphorelay involved in regulating the slug versus culmination choice during the multicellular developmental program of Dictyostelium discoideum. When the relay is active, slug migration is favored due to the activation of a cyclic AMP (cAMP) phosphodiesterase and the resultant lowering of the intracellular and extracellular levels of cAMP. Ammonia signaling represents one input into the DhkC phosphorelay, and previous studies indicated that the ammonium transporter C inhibits the relay in response to low ammonia levels.