Publications de Daniel Constam

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The TGF beta family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on ...

The Shc family of adaptor proteins are crucial mediators of a plethora of receptors such as the tyrosine kinase receptors, cytokine receptors, and integrins that drive signaling pathways governing proliferation, differentiation, and migration. Here, we rep ...

Tissue patterning during development relies on cell communication by secreted proteins and receptors that engage in complex signaling crosstalk to induce distinct cell behaviors in a context-dependent fashion. Here I summarize recent insights into basic me ...

Receptor binding of TGF-β and related ligands such as Activin-A requires cleavage of a furin site in their dimeric precursor proteins. Melanoma cells cleave one Activin-A subunit independently of furin and related proprotein convertases, raising questions ...

The secreted growth factor Activin-A of the transforming growth factor beta family and its receptors can promote or inhibit several cancer hallmarks including tumor cell proliferation and differentiation, vascularization, lymphangiogenesis and inflammation ...

The EGF-CFC gene cripto governs anterior-posterior (A-P) axis specification in the vertebrate embryo. Existing models suggest that Cripto facilitates binding of Nodal to an ActRII-activin-like kinase (ALK) 4 receptor complex. Cripto also has a crucial func ...

Mammalian Host-Cell Factor 1 (HCF-1), a transcriptional co-regulator, plays important roles during the cell-division cycle in cell culture, embryogenesis as well as adult tissue. In mice, HCF-1 is encoded by the X-chromosome-linked Hcfc1 gene. Induced Hcfc ...

The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions. Their knockout (KO) in mice resulted in strong and specific phenotypes demonstrating that, in vivo, these PCs are unique and essential during developmen ...

Axis formation and allocation of pluripotent progenitor cells to the germ layers are governed by the TGF-β-related Nodal precursor and its secreted proprotein convertases (PCs) Furin and Pace4. However, when and where Furin and Pace4 first become active ha ...

Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examin ...

The glycosylphosphatidylinositol (GPI)-anchored proteoglycan Cripto binds Nodal and its type I receptor Alk4 to activate Smad2,3 transcription factors, but a role during Nodal precursor processing has not been described. We show that Cripto also binds the ...

The invention relates to a system for detecting the presence of a convertase cleaving activity, the system comprising a molecule comprising a proteolytic cleavage site with the amino acid sequence -R-X1-X2-R-, wherein R represents the amino acid arginine, ...

In human, mutations in bicaudal C1 (BICC1), an RNA binding protein, have been identified in patients with kidney dysplasia. Deletion of Bicc1 in mouse leads to left-right asymmetry randomization and renal cysts. Here, we show that BICC1 is also expressed i ...

We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, ren ...

Cripto is a glycosylphosphatidylinositol (GPI)-anchored co-receptor of Nodal and several other transforming growth factor-beta (TGF-beta) family ligands. It contains an epidermal growth factor (EGF)-like motif and a Cripto-FRL1-Cryptic (CFC) domain, which ...

Loss of the RNA-binding protein Bicaudal-C (Bicc1) provokes renal and pancreatic cysts as well as ectopic Wnt/beta-catenin signaling during visceral left-right patterning. Renal cysts are linked to defective silencing of Bicc1 target mRNAs, including adeny ...

Daniel Constam

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Nodal.Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

Cellular Heterogeneity During Embryonic Stem Cell Differentiation to Epiblast Stem Cells Is Revealed by the ShcD/RaLP Adaptor Protein

Intracellular trafficking and signaling in development

Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma

Paracrine Activin-A Signaling Promotes Melanoma Growth and Metastasis through Immune Evasion

Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction

Epiblast-specific loss of HCF-1 leads to failure in anterior-posterior axis specification

Furin Is the Primary in Vivo Convertase of Angiopoietin-like 3 and Endothelial Lipase in Hepatocytes

Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst

Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex

Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation

Visualization of proprotein convertase activity in living cells and tissues

Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

Cripto localizes nodal at the limiting membrane of early endosomes

Comment on "Human dignity and gene editing"

Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA