Lab Website: http://linfishlab.webs.com

G protein signaling in zebrafish embryogenesis

Cell migration is a fundamental process that plays critical roles in early embryonic development, as well as in proper organ function and homeostasis later in life. Beyond early development, cell migration is vital to processes such as wound healing, immune responses, and tissue regeneration. Aberrant cell migration contributes to many pathological conditions, including birth defects, immune dysfunction and cancer metastasis.

The regulation of cell migration involves highly orchestrated signaling networks. One set of signaling molecules that contributes to this kind of regulation is the family of G protein-coupled receptors (GPCRs), which act through heterotrimeric G proteins. Our laboratory is interested in understanding how G protein signaling regulates cell migration in vivo, using zebrafish as animal model. The fact that these animals develop externally and are translucent makes it possible to carry out high-resolution imaging in live animals (see the links for the cool movies and images). We also exploit the powerful embryological, genetic, pharmacological and cellular tools available for the zebrafish system. As many cell types utilize similar strategies for migration, and similar mechanisms for, signaling, under physiological and pathological conditions, our study will provide new insights into the mechanisms that underlie morphogenetic processes during development. Moreover, they will have broad implications for our understanding of cellular processes as they occur in the context of pathobiology.

Current projects

Gastrulation: a critical period of life Gastrulation is an important process that transforms an embryo from a simple group of cells into a well-defined animal with a clear head, trunk and tail. During gastrulation, embryos develop multiple germ layers and organize these into the organ primordia of the embryo through four robust morphogenetic movements: epiboly, internalization, internalization and extension. Each of these movements is highly conserved among vertebrates, and is key to narrowing and extending the embryonic axes during vertebrate gastrulation. Our laboratory and others have shown that GPCR signaling is critical for these movements. Currently, we are focusing on understanding the how GPCR signaling regulates the coordinated migration of mesodermal and endodermal cells during gastrulation, as such migration is likely to influence organ development and function.

Migration of the posterior lateral line primordium: a model of collective migration

The lateral line is a sensory system that detects water movement and is found in aquatic vertebrates. It comprises a set of mechanosensory organs (neuromasts) that are arranged in specific patterns on the surface of the animal. The neuromasts are formed from the migrating posterior lateral line primordium (PLLP), which is comprised of 100 cells that migrate as a cohesive cell cluster from head to tail along the flanks of the animal body. The PLLP displays morphological polarity, with distinct leading and trailing regions. During migration, subsets of cells in the trailing regions periodically separate from the cluster and are deposited along the trunk to form neuromasts. We are currently investigating the signaling mechanisms that control PLLP migration and neuromast formation.

Migration of primordial germ cells (PGCs): A model of individual cell migration

PGCs are precursors of sperm and eggs, which transmit genetic information to the next generation. In many organisms, PGCs migrate a long distance from their sites of specification to the region in which the gonad develops. The mechanisms that regulate the motility and directed migration of PGCs are relevant to other cell migrations that occur in the contexts of both normal development and disease. Thus PGC migration in zebrafish has emerged as a powerful model system for investigating cell migration in a developing organism. Chemoattractants provide guidance cues that facilitate the directional migration of PGCs, and it is well established that the chemokine Sdf1a and its cognate G protein-coupled receptors, Cxcr4b and Cxcr7, are critical for proper PGC migration. However, which of the G proteins and their downstream effectors contribute to this process remains largely unknown. Our goal is to define the G protein signaling pathways that are involved in PGC migration.

PubMed link

Department/Program Affiliations:
Anatomy and Cell Biology
Molecular Medicine