Hélène Cousin

Hélène Cousin, Ph.D.

Research Assistant Professor

Hélène Cousin

Office phone: 413-577-1156

Lab phone: 413-545-3739

Fax: 413-545-6326

Email: hcousin [at] vasci [dot] umass [dot] edu

Office location: 427N ISB

Mailing address:

661 Northpleasant street
Amherst, MA 01003

Ph.D.:  Université Paris VI, France (2000)

Postdoctoral training: University of Virginia,  Charlottesville VA; University of Massachusetts, Amherst, MA.

Courses:
ANIML SCI  220
- Anatomy and Physiology
ANIML SCI 297W - ST-Poultry Management II
ANIML SCI  697J - Cells, Genes, and Development
ANIML SCI  792 - Seminar: Animal Biotechnology & Biomedical Sciences
BIOLOGY 580 - Developmental Biology

Link to advising:

During development, extensive cell movements change the shape the embryo from a sphere with a radial symmetry to an elongated, multilayered and asymmetric organism. The first morphogenetic movement occurs at gastrulation, when the mesoderm (that gives rise to the muscles, heart and blood vessels) and the endoderm (that gives rise to the gut, liver, pancreas etc…) are internalized. During neurulation, the neural tissue “rolls up” into a tube and the somitic mesoderm (future muscles) undergoes segmentation and rotation. After neurulation is complete, the dorsal most cells called neural crest cells  undergo extensive migrations in the embryos and give rise to the melanocytes, and ganglia in the trunk and to most of the facial structures in the head. All these cell movements require the extracellular matrix (ECM) and transmembrane proteins capable of mediating cell-matrix (like integrin) and cell-cell (like cadherins) adhesion. These transmembrane proteins can also activate or be activated by intracellular signals to direct or modulate these events.

Three ways to study CNC migration in Xenopus laevis in real time.

 

Cell movement during frog embryonic development.

           We are investigating the mechanisms that control the morphogenetic movements with a particular emphasis on Cranial Neural Crest cell (CNC) migration in the frog Xenopus laevis. So far, we have identified the ECM protein fibronectin and the transmembrane proteins integrin α5β1, the ADAM metalloproteases as key players during CNC migration. We are currently studying the exact role of each of these ADAMs during CNC migration in vivo using classical embryology approaches such as grafts (Figure 1) combined with the latest molecular biology tools available (knock down, microarray etc…). We are also searching for the physiological substrates of these ADAMs and their involvement during these processes. In parallel, we are exploring the potential roleof these ADAMs during other morphogenetic movements. We are also studying the peculiar role of their cytoplasmic domain during these events. The cytoplasmic domain of ADAM13 is cleaved by the protease gamma secretase, and is transported into the nucleus where it regulate the transcription of genes involved in CNC migration, including the protease Calpain8b.  We are currently investigating the mechanisms that control each of these steps.

 

 

 

ADAMs function during Zebrafish development.

While the frog system allowed us to decipher previously unknown function of ADAM during CNC migration, a few observations suggest that this function may have diverged in other vertebrates. First, the Xenopus CNC migration assay shows that while the cytoplasmic domain of C.elegans, zebrafish and opposum ADAM13 is functionally equivalent to Xenopus ADAM13, the mouse ADAM13 (aka ADAM33) is not (Cousin et al., 2011). Second, Xenopus CNC migration is very particular among the vertebrates. While most other species’ crest delaminates from the neural tube and migrate as a single cells from throughout the entire migration, Xenopus CNC migrate first as a cohesive sheet of cells before undergoing EMT and migrating as single cells. Since we showed that meltrin are necessary for the initiation of CNC migration, it is possible its function is only required for the “sheet” migration but not the single cell migration. The absence of effect of ADAM13 and 19 knock down on CNC migration in vitro seems to support this hypothesis (Cousin et al, 2012).

 

Zebrafish neural crest is visualized in vivo in this Sox10::GFP trangenic line

Therefore, we are investigating the function of meltrins in a specie whose CNC migrate in a fashion that reflect mammalian CNC migration. The Zebrafish model is ideal for various reasons: 1- the embryos are readily amenable to microinjection (mRNA, morpholino), 2- the availability of many strain where GFP is expressed in specific tissues (ex: Sox10::GFP line express GFP in neural crest) allows a quick identification of phenotype by simple live imaging (Figure 2). The inhibition of the ADAM expression using antisens morpholino technology will answers two of fundamental questions: 1- Are ADAM involved in CNC migration in vertebrates other than Xenopus? 2- Are ADAM involved at a later stage of craniofacial development?

Ji YJ, Hwang Y-S, Mood K, Cho H-J, Lee H-S, Winterbottom E, Cousin H, Daar IO.  2014.  EphrinB2 affects apical constriction in Xenopus embryos and is regulated by ADAM10 and flotillin-1.. Nat Commun. 5:3516.
Cousin H, Alfandari D.  2011.  ADAM and cell migration: the unexpected role of the cytoplasmic domain. Médecine sciences : M/S. 27(12):1069-71.
Alfandari D, Cousin H, Marsden M.  2010.  Mechanism of Xenopus cranial neural crest cell migration.. Cell adhesion & migration. 4(4):553-60.
Neuner R, Cousin H, McCusker C, Coyne M, Alfandari D.  2009.  Xenopus ADAM19 is involved in neural, neural crest and muscle development.. Mechanisms of development. 126(3-4):240-55.
Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, Black SJ, Alfandari D.  2009.  Cloning and expression of ADAM-related metalloproteases in equine laminitis.. Veterinary immunology and immunopathology. 129(3-4):231-41.
Alfandari D, McCusker C, Cousin H.  2009.  ADAM function in embryogenesis.. Seminars in cell & developmental biology. 20(2):153-63.
McCusker C, Cousin H, Neuner R, Alfandari D.  2009.  Extracellular cleavage of cadherin-11 by ADAM metalloproteases is essential for Xenopus cranial neural crest cell migration.. Molecular biology of the cell. 20(1):78-89.
Cousin H, Desimone DW, Alfandari D.  2008.  PACSIN2 regulates cell adhesion during gastrulation in Xenopus laevis.. Developmental biology. 319(1):86-99.
Cousin H, Gaultier A, Bleux C, Darribère T, Alfandari D.  2000.  PACSIN2 is a regulator of the metalloprotease/disintegrin ADAM13.. Developmental biology. 227(1):197-210.
Name Phone Office
Grennon , Joseph Undergraduate Student 413-545-3739 455 ISB
Loughman , Katie Undergraduate Student 545-3739 455 ISB
McLinden , Gretchen Undergraduate Student 413-545-3739 455 ISB
Pack , Rebeka Undergraduate Student 413-545-3739 455 ISB
Former Lab Personnel